Transcript of "Alcohols Contribution to Compromised Immunity"
Alcohol’s Contribution to
GYONGYI SZABO, M.D., PH.D.
Alcoholics frequently suffer from infectious diseases and have increased rates of
some cancers, indicating that alcohol impairs the immune system, which protects the
body against this type of damage. Alcohol interferes with the functions of many of
the cells and molecules that are part of the immune system. For example, alcohol
inhibits the functions of the cells that ingest and destroy invading microorganisms
(i.e., neutrophils, monocytes, and macrophages). Both acute and chronic alcohol
exposure also alter the production of signaling molecules that help coordinate the
immune response (i.e., cytokines). Finally, alcohol adversely affects the functions of
the cells that mediate the immune response against specific microorganisms and
long-term immunity (i.e., T cells and B cells). As a result, alcoholics have an
increased susceptibility to diseases caused by bacterial infections, such as
tuberculosis and pneumonia. Alcoholics also may be more susceptible to infections
from the virus that causes AIDS. In addition, alcohol intoxication can exacerbate the
immune suppression that occurs after traumatic injuries. KEY WORDS: immune system;
immune disorder; immune response; AODE (alcohol and other drug effects); cytokines;
inflammation; oxygen radicals; bacterial disease; HIV infection; trauma; injury; pathologic
process; literature review
increased risk of developing tumors, THE IMMUNE SYSTEM—AN
he immune system serves as the
body’s defense against infections particularly in the head, neck, and OVERVIEW
by microorganisms; damage upper gastrointestinal tract. Although
caused by other foreign substances; alcohol-induced malnutrition—includ- The immune system has two main
and the uncontrolled, tumorous growth ing vitamin deficiencies—and ad- arms: innate, or nonspecific, immunity
of the body’s own cells. Impairment of vanced liver cirrhosis likely contribute and acquired, or specific, immunity.
this system can increase a person’s to some abnormalities in the immune Innate immunity exists before the
risk for developing various illnesses, system of alcoholics, alcohol itself body is exposed to a pathogen for the
including infectious diseases, such as also is a potent modulator of immune first time. Moreover, this system does
tuberculosis, and certain types of can- functions. Interestingly, not only not respond to specific pathogens but
cer. Alcohol can modulate this de- chronic alcohol abuse but also single- instead responds to any pathogen it
fense, and clinicians have known for a episode (i.e., acute) and/or moderate encounters. For example, the cells
long time that chronic alcohol abusers alcohol consumption can affect the involved in innate immunity immedi-
have an impaired immune system. immune system. ately attack any kind of bacterium or
This impairment manifests itself in This article briefly reviews the
several ways. For example, alcoholics main features and components of the GYONGYI SZABO, M.D., PH.D., is a
are prone to infections by various immune system and summarizes some research associate professor of medi-
disease-causing microorganisms (i.e., of the consequences and mechanisms cine in the Department of Medicine,
pathogens); have a decreased ability to of alcohol use on the body’s defense University of Massachusetts Medical
fight these infections; and have an against pathogens. Center, Worcester, Massachusetts.
30 ALCOHOL HEALTH & RESEARCH WORLD
Alcohol and Compromised Immunity
virus that enters the body, whether it is cules that function cooperatively to nize and bind to antigens. Like T cells,
the first or second infection by that mount a complex host defense and each B cell also recognizes only one
organism. Acquired immunity, in thereby amplify and focus the protection specific antigen and becomes activated
contrast, is activated only after the offered by the innate immunity. The when it comes into contact with it.
body is exposed to a pathogen for the most important cells involved in ac- Most activated B cells develop into so-
first time. In addition, the acquired quired immunity are T lymphocytes, or called plasma cells, which secrete their
response is specific to one particular T cells, and B lymphocytes, or B cells. antibodies into the blood or lymph.
pathogen. For example, when Myco- These cells circulate in the blood or There the antibodies can bind to their
bacterium tuberculosis, the bacterium reside in special lymphoid tissues (e.g., target antigens (e.g., a virus or a virus-
that causes tuberculosis, enters the the spleen, lymph nodes, and tonsils), infected cell) and thus mark them for
body, the contact with that pathogen where they can encounter antigens and destruction. Other B cells become
activates cells involved in acquired initiate an immune response. memory cells, which help the body
immunity. These activated cells attack T cells and B cells are the corner- fight a second infection by the same
only M. tuberculosis and no other stones of two types of immune re- pathogen more expeditiously.
bacteria or viruses. The activated cells sponses, the cell-mediated immunity The T-cell and B-cell responses are
also generate a kind of immune “mem- and the antibody-mediated (i.e., hu- not independent of each other, however,
ory” that allows the body to fight a moral) immunity. The cell-mediated but are intricately intertwined. Thus, B
second infection by the same pathogen immunity relies primarily on T cells cells that have bound an antigen serve
even faster and more efficiently. that are activated by exposure to anti- as antigen-presenting cells that can
The elements of innate immunity gen-presenting cells (e.g., monocytes, activate a T-cell response. Moreover, B
include white blood cells that ingest and macrophages, and B cells). Each anti- cells and T cells communicate with each
destroy microorganisms (i.e., phago- gen-presenting cell displays only one other and with other immune cells by
cytes); certain proteins that circulate in antigen (e.g., a viral protein) on its secreting numerous cytokines that can
the blood, called the complement1 surface and thus stimulates only T influence various components of both
system; and signaling molecules (i.e., cells that recognize this specific anti- the nonspecific and specific immune
cytokines) that are produced and secret- gen. The activated T cell then can responses. For example, some T cells
ed by some of the phagocytes. Several bind to other cells carrying the same produce cytokines that stimulate their
different types of phagocytes exist, with antigen (e.g., virus-infected cells) and own activity or that of other T cells.
specific functions as follows: initiate their destruction. Several sub- Other subgroups of T cells secrete cy-
populations of T cells have specific tokines that inhibit the cell-mediated
• Neutrophils ingest and thereby de- functions in the complex chain of
stroy pathogens, primarily invading and humoral immunity and thus prevent
events occurring during an immune an excessive reaction of the immune
bacteria. response: system. Finally, some T-cell–derived
• Monocytes that circulate in the • Helper T cells produce and secrete cytokines enhance B-cell multiplication,
blood or that have entered the cytokines that stimulate the activity differentiation, and antibody production.
tissues (i.e., macrophages) ingest of other immune cells. The largest family of cytokines are the
and destroy a variety of foreign interleukins (IL’s), which are produced
substances and microorganisms. • Cytotoxic T cells recognize anti- in various cell types and have numerous
Monocytes also exhibit pathogen- gens on the surface of virus-infect- functions (see table).
derived proteins and other mole- ed or transplanted cells and destroy The following example may help
cules (i.e., antigens) on their surfaces these cells. illustrate some of the complex interac-
in order to activate other cells in tions that take place during an immune
• Suppressor T cells inhibit other
the immune system. Finally, mono- immune responses, thereby pre- response. When a person sustains a
cytes and macrophages secrete venting overreaction of the im- small injury, such as a cut, bacteria can
cytokines that help regulate im- mune system. enter the body and the bloodstream
mune system activity. through the wound. Phagocytes (e.g.,
• Delayed-type hypersensitivity T monocytes and neutrophils) patrolling
• Natural killer (NK) cells recognize cells produce cytokines that induce
and eliminate cells in the body that the blood encounter some of these
a localized inflammatory response
have been infected by parasites or bacteria; identify them as foreign to
and attract macrophages and cyto-
that have turned into cancer cells. the body; and engulf, ingest, and de-
toxic T cells to that site to elimi-
stroy them. During the intracellular
The elements of acquired immunity nate the antigen.
breakdown of the ingested bacteria,
include numerous cell types and mole- The B cells produce the humoral the phagocytes generate small proteins
immunity. These cells carry immune or protein fragments that serve as
For a definition of this and other technical
terms used throughout this article, see the proteins (i.e., antibodies, or immuno- antigens. The phagocytes display these
central glossary, pp. 93–96. globulins) on their surface that recog- antigens on their cell surface, together
VOL. 21, NO. 1, 1997 31
Important Cytokines of the Immune System
Cytokine Primary Source Principal Functions
Interferon alpha (IFN-α) Macrophages Induces protection against viral infections;
activates macrophages; and inhibits the growth
of various cell types
Interleukin 1 (IL-1) Macrophages and other cells Produces inflammatory responses; induces
fever; stimulates proliferation of helper T cells;
and promotes B-cell growth and differentiation
Interleukin 6 (IL-6) Macrophages, T cells, and other cells Promotes maturation of stimulated B cells to
antibody-secreting plasma cells; acts with other
cytokines to stimulate immature and mature T
cells; and stimulates production of complement
factors and other mediators of inflammatory
Tumor necrosis factor alpha Macrophages, T cells, natural killer (NK) Promotes inflammatory responses; stimulates
(TNF-α) cells, and other cells neutrophils and macrophages; induces fever;
and induces macrophages to produce IL-1,
IL-6, and TNF-α
Interleukin 10 (IL-10) Macrophages and T cells Inhibits T-cell proliferation; reduces production
of inflammatory cytokines; and promotes B-cell
proliferation and antibody secretion
Interleukin 12 (IL-12) Monocytes and macrophages Activates NK cells; activates a subtype of T
cells (i.e., CD4 T cells); and induces the cell-
mediated (i.e., Th1) immune response
Transforming growth factor beta Macrophages and T cells Inhibits T-cell proliferation; reduces production
(TGF-β) of inflammatory cytokines; augments B-cell
proliferation and antibody secretion; and
promotes collagen production
Interleukin 8 (IL-8) Macrophages Attracts neutrophils to the site of an infection
Interferon gamma (IFN-γ) T cells Induces protection against viral infection;
stimulates macrophages and neutrophils;
enhances expression of major histocom-
patibility complex (MHC) proteins on many
cells; and promotes B-cell and T-cell
Interleukin 2 (IL-2) T cells Stimulates proliferation of T cells; enhances
activity of NK cells; and stimulates B-cell
proliferation and antibody production
Interleukin 4 (IL-4) A subtype of T cells (i.e., CD4 T cells) Stimulates T-cell growth; induces B-cell
activation and growth; and modulates antibody
production by B cells
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Alcohol and Compromised Immunity
with certain of their own proteins B cells. Alcohol can interfere with Increased neutrophil chemotaxis
known as major histocompatibility both phases of the immune response. even occurred in rats that received a
complex (MHC) proteins. In addition one-time alcohol injection. In contrast,
to the phagocytes, proteins of the com- Alcohol’s Effects on the Kupffer cell chemotaxis decreased
plement system also recognize the in- Inflammatory Response under the same conditions. These
vading bacteria and bind to proteins on results suggest that alcohol can differ-
the bacterial surface. This binding trig- Effects on Phagocytic Cells. During entially affect the functions of various
gers several biochemical processes an inflammatory response, chemical phagocytic cell types. Studies with
that eventually lead to the destruction substances released by cells at the site cultured human cells, however,
of the bacteria. of the infection induce phagocytes to demonstrated decreased neutrophil
T cells circulating in the blood migrate from their normal locations chemotaxis after the cells were ex-
recognize phagocytes simultaneously in the bloodstream or the tissues to posed to alcohol.
displaying antigens and MHC proteins. the site of the inflammation. This Chronic as well as acute alcohol
The T cells bind to the phagocyte- process is called chemotaxis. Various consumption also reduces the ability
bound antigens through the help of substances can serve as chemotactic of phagocytes to ingest and break
docking molecules, called T-cell re- agents, including activated compo- down pathogenic bacteria. For exam-
ceptors. The activated T cells multiply nents of the complement system, a ple, cultured human monocytes ex-
and begin secreting cytokines, which, group of white blood cell-derived posed to alcohol showed reduced
in turn, activate cytotoxic T cells that proteins called leukotrienes, and other phagocytic functions; moreover, the
can then recognize, bind to, and de- proteins produced by immune cells cells produced less of a receptor pro-
stroy cells infected by the invading (i.e., chemokines, such as interleukin- tein that is required for the ingestion
bacteria. 8 [IL-8]). The neutrophils and mono- of antibody-coated particles. In mice,
Parallel to the T-cell response, the cytes recruited from the bloodstream both short-term and long-term alcohol
B cells mount another line of defense must adhere to and migrate through feeding reduced the phagocytic ability
against the invading bacteria. Thus, the cell layer lining the blood vessels of macrophages residing in the mem-
antibodies on the B-cell surface recog- at the site of the infection, ingest the brane lining the abdominal cavity.
nize and bind to antigens on the bacte- microorganisms, and destroy the in- Thus, abnormal neutrophil adherence
rial surface. This binding activates the gested pathogens using specific en- and chemotaxis, as well as reduced
B cells, which then differentiate into zymes or toxic, oxygen-derived free phagocytic function of macrophages,
plasma cells that secrete large amounts radicals. may contribute to the impaired de-
of antibodies. The antibodies are dis- Alcohol can affect this sequence of fense against microorganisms ob-
tributed throughout the bloodstream events at several levels. Alcohol’s served after alcohol consumption.
and bind to the bacteria wherever they effects on phagocyte adhesion to the
encounter them, aided by proteins of blood-vessel walls and chemotaxis Effects on Inflammatory Cytokines.
the complement system. The antibody- were studied in chronically alcohol- Phagocyte contact with pathogens
covered bacteria clump together and fed rats. Neutrophils from these ani- induces the release of cytokines by the
become new targets for monocytes and mals exhibited increased levels of phagocytes that help initiate and
other phagocytes. CD18 molecules on their surface, maintain the inflammatory response
which are required for adhesion. and thus play a pivotal role in the
Furthermore, chemokines (e.g., IL-8) body’s immune defense. The most
ALCOHOL’S EFFECTS ON THE
secreted by macrophages residing in common inflammatory cytokines—
the liver (i.e., Kupffer cells) of the tumor necrosis factor alpha (TNF-α),
The body’s response to an invading alcohol-fed rats increased the chemo- IL-1, and IL-6—are primarily pro-
pathogen can be divided into two taxis of normal neutrophils. Increased duced by monocytes and macrophages
phases. The first phase is an inflam- infiltration of neutrophils into the (see figure). During an overwhelming
matory reaction, which protects the liver, in turn, can lead to liver injury. inflammatory response, however,
body from the immediate effects of Thus, an alcohol-induced increase in neutrophils, lymphocytes, and other
the infection. The inflammatory re- chemokine production by Kupffer tissue cells also can be sources of in-
sponse primarily involves phagocytic cells may lead to neutrophil accumu- flammatory cytokines. Excessive lev-
cells that help eliminate the pathogen, lation and thus to liver damage (e.g., els of these cytokines may cause
cytokines secreted mainly by these alcoholic hepatitis). This hypothesis is tissue damage, whereas reduced levels
phagocytes, and other molecules (e.g., consistent with observations that in may result in an insufficient immune
oxygen radicals) that assist in killing patients with acute alcoholic hepatitis, response.
the pathogen. The second phase, the IL-8 levels in the blood are elevated In chronic alcohol abusers, particu-
development of immunity to the and may be associated with neutrophil larly those with alcoholic liver dis-
pathogen, is mediated by T cells and accumulation in the liver. ease, the levels of TNF-α, IL-1, and
VOL. 21, NO. 1, 1997 33
rial antigens and thus may interfere
with the normal interaction of the cell-
mediated and humoral immunities.
The other cytokine controlling
(e.g., TGF-β, IL-10) (e.g., TNF-α, inflammatory reactions and T-cell
IL-1, IL-6) proliferation is TGF-β. In experiments
using cultured monocytes, physio-
logically relevant alcohol concentra-
tions2 activated both the baseline and
the bacterial antigen-induced TGF-β
activating production. Elevated TGF-β levels
Chemokines cytokines may have multiple implications for
(e.g., IL-8) (e.g., IL-12) immune-system functioning, includ-
ing inhibition of inflammatory cyto-
kine production by monocytes and
Other factors (e.g., proteins other cells, inhibition of T-cell prolif-
involved in blood clotting, eration, and augmentation of the
(e.g., oxygen radicals, nitric oxide)
proteins stimulating the humoral immune response. As a re-
growth of other cells)
sult, the drinker becomes more sus-
ceptible to infections and exhibits
decreased immune system activity in
Monocyte/macrophage-derived substances potentially affected by alcohol. Mono-
cytes and macrophages produce numerous substances that initiate and regulate
eliminating infections. In addition,
inflammatory reactions; attract other immune cells (i.e., chemokines); stimulate T elevated TGF-β levels promote colla-
cells; help in the elimination of pathogens, such as bacteria; and perform other gen production. Collagen molecules
functions throughout the body. Alcohol may interfere with the production and se- normally form the fibers making up
cretion of all these substances, thereby impairing the body’s immune response. tendons and ligaments. However,
excessive collagen production result-
IL = interleukin; TGF-β = transforming growth factor beta; TNF-α = tumor necrosis factor alpha.
ing from alcohol-induced TGF-β may
result in abnormal collagen deposits
IL-6 in the blood are significantly fense against microorganisms, im- in the liver that have been implicated
elevated. These increased cytokine paired inflammatory cytokine produc- in the development of some types of
levels may contribute to most of the tion after acute alcohol exposure alcoholic liver disease.
signs and symptoms observed in pa- significantly compromises the body’s Alcohol also increases the produc-
tients with alcoholic hepatitis (e.g., defense system. tion of nonprotein regulatory
generally increased metabolism, fever, molecules that inhibit the antigen-
weight loss, elevated levels of pro- Effects on Immunoregulatory presenting capacity of monocytes,
teins produced in the liver, and mark- Cytokines. The initial inflammatory inflammatory cytokine production,
ers of malnutrition). It is unknown, response to pathogens normally is and T-cell proliferation.
however, which cells cause the eleva- turned off by regulatory cytokines By increasing the levels of these
ted inflammatory cytokine production whose production typically is induced substances as well as of IL-10 and
in alcoholics. in a later phase of the infection. The TGF-β, alcohol can interfere with
Acute, moderate alcohol consump- most studied immunoregulatory cy- the body’s normal defense against
tion, in contrast, transiently reduces tokines are IL-10 and transforming invading microorganisms in two
the pathogen-induced production of growth factor beta (TGF-β), both of ways: by reducing inflammatory-
inflammatory cytokines. For example, which are produced by macrophages cytokine production and by inhibit-
cultured human monocytes exposed to and T cells. IL-10 promotes humoral ing T-cell proliferation.
alcohol before being stimulated with immunity and inhibits cell-mediated
various bacterial antigens produced immunity by reducing the production 2
The alcohol concentrations used in these
lower-than-normal levels of TNF-α, of several cytokines, including inflam- experiments were 10 to 100 millimoles per liter
IL-1, and IL-6. Similarly, the TNF-α matory cytokines, and by preventing (mmol/L). Concentrations of 25 mmol/L
levels produced in response to a chal- the multiplication (i.e., proliferation) approximate blood alcohol levels of 0.1 per-
lenge with a bacterial antigen were of T cells. Acute alcohol exposure cent, the legal limit for driving in many States.
Concentrations of 100 mmol/L correspond to
decreased in mice that had received a increases IL-10 production in cultured blood alcohol levels of approximately 0.4
single dose of alcohol. Considering human monocytes both in the absence percent, which are sometimes seen in alco-
the pivotal role of TNF-α in the de- and presence of stimulation by bacte- holics after acute alcohol consumption.
34 ALCOHOL HEALTH & RESEARCH WORLD
Alcohol and Compromised Immunity
Effects on Oxygen-Radical Production. cells in the blood, in the thymus—the reduced T-cell proliferation, accom-
Oxygen radicals (e.g., superoxide anions gland where T cells mature—and in panied by an enhanced humoral im-
and hydrogen peroxide) are unstable the spleen, where immune reactions munity marked by increased antibody
oxygen-containing molecules that are initiated. The mechanism underly- levels. This shift in the immune re-
readily interact with other molecules ing the alcohol-induced decrease in T- sponse likely impairs the body’s defense
in a cell. Oxygen radicals produced by cell numbers still is unknown. Some against bacterial infections requiring a
macrophages and other phagocytes researchers have suggested that acute predominantly cell-mediated immune
play a crucial role in destroying micro- alcohol exposure induces programmed response, such as infections with M.
organisms, especially in the lungs. cell death, or apoptosis, in immature T tuberculosis or Listeria monocytogenes,
Researchers found that macrophages cells in the thymus. Acute alcohol which are discussed in the section
in the lungs of acutely or chronically exposure also results in increased “Consequences of Alcohol’s Effects on
alcohol-fed rats produced fewer super- apoptosis of mature lymphocytes and the Immune System.” Alcohol’s effects
oxide anions and less hydrogen per- monocytes in the blood. on the antibody-producing B cells is
oxide than did macrophages from Alcohol also may reduce the ability discussed in more detail in the follow-
non-alcohol-exposed rats. Further- of lymphocytes to proliferate and differ- ing section.
more, the lung macrophages produced entiate adequately after they have been
and secreted less nitric oxide, another activated by an antigen. Moreover, the Effects on B Cells. A characteristic
molecule with characteristics and number and function of delayed-type immune-system aberration observed in
functions similar to those of oxygen hypersensitivity T cells is reduced in alcoholics is the elevation of antibody
radicals. The alcohol-induced decreas- alcoholics. As a result, the immune levels in the blood. Similarly, acute
es in the macrophages’ production of response to certain antigens and infec- alcohol consumption in mice increased
oxygen radicals and nitric oxide could tions is depressed. How alcohol affects antibody production in response to
undermine the body’s defense against T-cell proliferation is not well under- certain chemical substances. Because
bacteria. This mechanism could con- stood. In chronically alcohol-fed rats, antibodies are produced by B cells,
tribute to the high incidence of tuber- the T cells fail to proliferate adequately these observations indicate that alcohol
culosis in alcoholics. (For more in response to stimulation by IL-2. The alters either the number or function of
information on the association of results of other investigations imply B cells. To date, conflicting results
alcohol use and tuberculosis, see side- that decreased T-cell proliferation may exist regarding these two alternatives.
bar, pp. 39–41.) be a consequence of the impaired Thus, clinical studies in humans found
Alcohol-induced overproduction of function of accessory cells (e.g., anti- that the absolute number of B cells did
oxygen radicals in the liver, in con- gen-presenting cells) after alcohol use. not differ between alcoholics and non-
trast, may contribute to the develop- For example, the interaction of T cells alcoholics, but that B-cell functioning
ment of alcoholic liver damage. In rats with antigen-presenting monocytes or appeared to be altered in alcoholics. In
that received alcohol infusions for 1, 3, macrophages requires the presence of contrast, in mice that had been fed
or 5 hours, for example, the Kupffer several proteins on the surfaces of both alcohol for 14 days, the number of B
cells in the liver produced and secreted
the T cells and the antigen-presenting cells in the spleen had decreased five-
increased levels of superoxide anions,
cells (e.g., T-cell receptors and MHC fold. Equally contradictory were the
whether or not the cells were activated
molecules). The production of some findings regarding B-cell functioning:
by contact with pathogens. Together,
of these proteins also is altered in Whereas clinical studies demonstrated
these observations imply that alcohol
alcohol-exposed cells. Finally, reduced elevated antibody levels in alcoholics,
may have a dual negative effect on the
T-cell proliferation may be attributed tissue-culture experiments to investi-
body’s oxygen-radical production.
to the increased production of immuno- gate these observations found that
First, alcohol may inhibit oxygen-
radical and nitric oxide production in regulatory cytokines (e.g., IL-10 and alcohol inhibited the B-cells’ antibody
macrophages in the lung, where these TGF-β) caused by alcohol. secretion.
substances are essential for killing Overall, the effects of both acute One possible explanation for these
microorganisms. Second, alcohol may and chronic alcohol exposure result in conflicting findings is that alcohol inter-
increase oxygen-radical production in a weakened cell-mediated immune feres only with some aspects of B-cell
the liver, where these molecules may response. Several diseases are char- functioning. For example, B cells do
cause tissue damage. acterized by a reduction in the cell- not respond to all antigens in the same
mediated immunity and a concomitant manner. In response to some antigens,
increase in the humoral immunity. B cells require the assistance of cy-
Alcohol’s Effects on Immunity Similarly, the immunological abnor- tokines secreted by T cells (i.e., T-
Effects on T Cells. Alcoholics and malities observed after both chronic cell–dependent responses), whereas in
laboratory animals chronically ingest- and acute alcohol consumption appear response to other antigens, T-cell acti-
ing alcohol have lower-than-normal to be consistent with a decreased cell- vation is not required (i.e., T-cell–inde-
numbers of all subpopulations of T mediated immunity characterized by pendent responses). Alcohol appears to
VOL. 21, NO. 1, 1997 35
affect these responses differently, vival of certain T-cell subpopulations. coccal pneumonia compared with the
because B cells in the spleens of alco- Although alcohol in tissue culture general population, and despite the use
hol-consuming animals showed im- experiments had no effect on the abili- of antibiotics, the mortality among
paired proliferation during a T-cell– ty of T cells to produce IL-2, it likely these patients remains disturbingly
dependent response but normal prolif- interferes with the T-cell response to high (15 to 77 percent). Researchers
eration during a T-cell–independent IL-2. The potential intracellular mecha- have used mice to study some of the
response. Similarly, alcoholics exhibit- nisms underlying these effects, how- mechanisms underlying the increased
ed an intact T-cell–independent anti- ever, remain unknown. susceptibility to infections by infect-
body response after administration of a Alcoholics exhibit decreased blood ing the animals with Listeria monocy-
specific antigen. Thus, alcohol may levels of IFN-α, IFN-γ, and IL-2.3 In togenes, a bacterium that among other
interfere with antibody production particular, the reduction of IFN-γ levels symptoms, causes liver damage in the
indirectly by inhibiting the production may be a key element underlying many animals. Mice that received an alcohol-
of certain T-cell–derived cytokines of the immune alterations observed in containing diet for 7 days before be-
required for B-cell function. The com- alcoholics because this cytokine, in ing infected with Listeria developed
plexity of alcohol’s effects on B cells is concert with the macrophage-derived greater liver damage than control
underscored further by findings that IL-12, is crucial for induction of the animals that had received no alcohol.
alcohol impairs B-cell proliferation in cell-mediated immune response. Conse- Although the alcohol treatment did not
response to the T-cell–derived cytokine quently, in the absence of appropriate impair the migration of phagocytes to
IL-4 but not in response to the T-cell- IFN-γ stimulation in alcoholics, a the liver, it did impair the animals’
derived cytokine IL-2. preferential induction of the humoral ability to inhibit Listeria growth. Thus,
immune response could occur. The even alcohol-fed mice that should have
Effects on Natural Killer Cells. NK accompanying lack of an appropriate been able to stave off the infection,
cells are a type of white blood cell cell-mediated immune response would because they had previously been im-
involved in the destruction of virus- make the alcoholics more susceptible munized with Listeria, had 100 times
infected and cancerous cells. Conse- to infections that require a T-cell re- more Listeria organisms in their livers
quently, NK cells play an important sponse. Furthermore, decreased IFN-γ than did nonalcohol-treated controls.
role in preventing tumor development. levels likely contribute to additional The body’s anti-Listeria defense is
Chronic alcohol consumption is asso- cytokine abnormalities (e.g., altered largely T-cell dependent and requires
ciated with increased incidence of IL-12 levels), thereby further impair- interactions between specific antigens,
tumors, suggesting that NK cell activ- ing the cell-mediated immune response. T cells, and phagocytic cells as well as
ity may be impaired. In laboratory IFN-γ and IL-12 induction. However,
animals, chronic alcohol administra- CONSEQUENCES OF ALCOHOL’S the exact roles of alcohol-induced aber-
tion reduced the number and activity EFFECTS ON THE IMMUNE SYSTEM rations in immune-cell interactions,
of NK cells. Tissue-culture experi- antigen-presenting cell function, and
ments, in contrast, produced conflict- IFN-γ and/or IL-12 production remain
ing results, demonstrating that alcohol Increased Susceptibility to to be determined.
had either an inhibitory effect or no Bacterial Infections Alcohol use also impairs the body’s
effect on NK cell activity. Finally, defense against pathogens infecting the
acute alcohol consumption temporari- Alcoholics are considered “immuno- lungs, such as pneumonia-causing bacte-
ly reduced the ability of rats to elimi- compromised hosts” because the inci- ria (e.g., pneumococci, Klebsiella pneu-
nate certain tumor cells and prevent dence and severity of infections are moniae, and Legionella pneumophila)
the development of tumor metastases. increased in these patients. Infections and M. tuberculosis. For example, in rats
with pathogens that reside within the infected with pneumococci, the animals’
Effects on Cytokines. Cytokines pro- host’s cells and cause diseases such as susceptibility to lethal pneumonia in-
duced by lymphocytes (i.e., lympho- pneumonia or tuberculosis are espe- creased if they received alcohol for 1
kines, such as IL’s and interferons cially prevalent. Thus, alcoholics have week before the infection. Moreover, the
[IFN’s]) regulate the functions of an increased incidence of pneumo- alcohol-fed rats experienced an increased
immune cells as well as nonimmune spread of the pneumococci from the
cells (e.g., nerve cells and cells of The discrepant observations that alcohol did lungs through the bloodstream compared
not affect the cells’ ability to produce IL-2 in
hormone-producing organs). The tissue culture experiments, whereas alcoholics with non-alcohol-treated rats and also
effects of either chronic or acute alco- show decreased IL-2 levels in the blood likely failed to eliminate the pneumococci from
hol use on cytokine production and can be attributed to the fact that tissue culture the blood. Other studies investigating
function, however, are only partially experiments monitor the consequences of acute alcohol’s effects on the susceptibility to
alcohol exposure, but the findings in alcoholics
understood. IL-2 is one of the most reflect the effects of chronic alcohol exposure.
infections with Klebsiella pneumoniae
important T-cell–produced cytokines; However, this hypothesis has not been investi- and Legionella pneumophila indicated
it promotes the proliferation and sur- gated in detail. that chronic alcohol treatment suppressed
36 ALCOHOL HEALTH & RESEARCH WORLD
Alcohol and Compromised Immunity
the production and/or function of neu- Current knowledge strongly sug- tant role in this process. Thus, acute
trophils and macrophages. Moreover, gests that alcohol use—potentially alcohol consumption before sustaining
treatment with a protein factor that stimu- both acute and chronic—can increase a traumatic injury can affect a patient’s
lates neutrophil production ameliorated a person’s susceptibility to HIV infec- TNF-α production and immunosup-
the alcohol-induced immunosuppression tion and contribute to alterations in pression after the injury as follows:
by recruiting more neutrophils to the the immune system that may result in
an accelerated progression of the • Within 0 to 3 days after the injury,
infection. However, further research is TNF-α production in the mono-
needed to elucidate the mechanism by cytes decreases in patients whose
Increased Susceptibility to HIV blood alcohol levels exceed 0.1
which alcohol may modulate the biol-
The relationship between alcohol use ogy of HIV infection. In addition to percent at emergency-room admis-
and susceptibility to infections with the its biological effects, alcohol use may sion, but increases in patients who
human immunodeficiency virus (HIV), increase the risk of HIV infection by have not consumed alcohol before
which causes acquired immune defi- modifying the drinker’s behavior. For sustaining the injury.
ciency syndrome (AIDS), is an actively example, factors such as increased • Later during the posttrauma period
evolving area of research. Although risk taking and uninhibited sexual (i.e., more than 6 days after the
ample data are available on the immu- behavior, which are associated with injury), the monocytes of alcohol-
nological abnormalities caused by both acute and chronic alcohol use, consuming trauma patients produce
alcohol use and HIV infection, respec- can contribute to an increased risk for higher TNF-α levels than the mono-
tively, knowledge concerning their HIV infection. cytes of non-alcohol-consuming
combined immunosuppressive effects trauma patients.
is more limited. Some researchers Consequences of Traumatic
have proposed that alcohol’s modula- Injuries • The increase in TNF-α production
tory effects on the immune system coincides with the development of
may increase the risk of initial HIV Traumatic injuries frequently are asso- posttraumatic immunosuppression,
infection as well as accelerate the ciated with severe suppression of the suggesting that acute alcohol con-
infection’s progression. Although this immune system, which can lead to over- sumption before sustaining major
hypothesis still awaits formal confir- whelming infections and may result in injuries increases the severity of
mation, several findings support alco- multiple organ failure and even death. the immunosuppression.
Alcohol intoxication not only increas-
hol’s proposed influence. For example,
es the risk of sustaining traumatic
one study found that HIV multiplied
injuries (e.g., in motor vehicle acci- CONCLUSIONS AND FUTURE
faster in blood cells isolated from binge
dents) but also may exacerbate trauma- DIRECTIONS
drinkers or subjects who had received
induced immunosuppression. Thus,
an acute alcohol dose than in cells from one study found that acutely intoxicat- Numerous research efforts have con-
people who had not been exposed to ed patients (i.e., those with blood firmed that both acute and chronic
alcohol (Bagasra et al. 1996). More- alcohol levels greater than 0.2 percent) alcohol use have profound regulatory
over, a case report of an HIV-infected who had sustained severe abdominal effects on the immune system. Studies
person demonstrated that the HIV injuries had a 2.6 times greater inci- in laboratory animals and in humans
infection progressed rapidly and that dence of infections than did patients have demonstrated that even acute,
the patient developed full-blown who had not consumed alcohol (Gen- moderate alcohol consumption can
AIDS after initiating heavy alcohol tilello et al. 1993). Moreover, rats that impair the body’s defense against
use (Fong et al. 1994). Finally, a study had received alcohol before sustaining bacteria and viruses, although these
of HIV-positive intravenous drug severe burn injuries exhibited a signifi- effects are likely only transient. The
users found that whereas alcohol use cantly impaired cell-mediated immunity clinical implications of such a transient
did not affect the proportion in the accompanied by an increased humoral immunodepression still need to be
blood of the T-cell subpopulation that immunity (i.e., elevated antibody pro- studied further. For certain types of
is the target of HIV infection, alcohol duction). Such an alcohol-related mod- infections (e.g., HIV and mycobacte-
use did correlate with increases in the ification of the immune system after ria), however, the failure of an appro-
proportion of another T-cell subpopu- sustaining a traumatic injury could priate initial immune response to
lation several years after the initial increase the patient’s risk of infections pathogens can have profound and po-
infection (Crum et al. 1996). Although and prolong the trauma-related sup- tentially prolonged effects on the im-
the clinical significance of this obser- pression of the immune system. mune system and the drinker’s health.
vation is still unclear, the findings The mechanism underlying trauma- Researchers and clinicians are gain-
suggest that alcohol consumption may induced immunosuppression has not ing further insight into the complex
exacerbate HIV-induced changes in yet been identified. However, the cy- mechanisms and consequences of
the immune system. tokine TNF-α clearly plays an impor- immunosuppression in chronic alco-
VOL. 21, NO. 1, 1997 37
holics. It is important, however, to BAGASRA, O.; BACHMAN, S.E.; JEW, L.; TAWA- JERRELS, T.; SAAD, A.J.; AND KRUGER, T.E.
dissect the effects caused by the body’s DROS, R.; CATER, J.; BODEN, G.; RYAN, I.; AND Ethanol-induced suppression of in vivo host
POMERANTS, R.J. Increased HIV type-1 replication defense mechanisms to bacterial infection. In:
chronic exposure to alcohol itself and in human peripheral blood mononuclear cells Friedman, H.; Klein, T.W.; and Specter, S., eds.
the effects of other alcohol-related induced by ethanol: Potential immunopathogenic Drugs of Abuse, Immunity, and AIDS. Vol. 335.
immunomodulatory conditions, such as mechanisms. Journal of Infectious Diseases New York: Plenum Press, 1993. pp. 153–158.
malnutrition, vitamin deficiencies, and 173:550–558, 1996.
KHORUTS, A.; STAHNKE, L.; MCCLAIN, C.J.;
alcoholic liver disease. Moreover, a BAUTISTA, A.P. Chronic alcohol intoxication LOGAN, G.; AND ALLEN, J.I. Circulating tumor
better understanding of the specific induces hepatic injury through enhanced macro- necrosis factor, interleukin-1 and interleukin-6
phage inflammatory protein-2 (MIP-2) produc- concentrations in chronic alcoholic patients.
immune system alterations caused by tion and intracellular adhesion melocule Hepatology 13:267–276, 1991.
chronic alcohol consumption is neces- expression in the liver. Hepatology 25:335–342, KRUGER, T.E., AND JERRELS, T.R. Potential role
sary for designing effective therapeutic 1997. of alcohol in human immunodeficiency virus
approaches to ameliorating immuno- BEN-ELIYAHU, S.; PAGE, G.G.; YIRMIYA, R.; infection. Alcohol Health & Research World
suppression in chronic alcoholics. AND TAYLOR, A.N. Acute alcohol intoxication
Researchers also are investigating suppresses natural killer cell activity and pro- MANDREKAR, P.; CATALANO, D.; AND SZABO, G.
the mechanisms underlying the differ- motes tumor metastasis. Nature Medicine 2: Human monocyte IL-10 production is increased
457–460, 1996. by acute ethanol treatment. Cytokines 8:567–
ential effects of chronic and acute
alcohol use on the immune system. CRUM, R.M.; DALAI, N.; COHN, S.; CELENTANO,
For example, the increased levels of D.D.; AND VLAHOV, D. Alcohol use and T NELSON, S.; SHELLITO, J.; MASON, C.; AND SUM-
lymphocyte subsets among injection drug users MER, W. Alcohol and bacterial pneumonia. Al-
inflammatory cytokines observed in with HIV-1 infection: A prospective analysis. cohol Health & Research World 16:73–86, 1992.
alcoholics contrast with the decreased Alcoholism: Clinical and Experimental
inflammatory response seen after Research 20:364–371, 1996. ROSELLE, G.A. Alcohol and the immune system.
Alcohol Health & Research World 16:16–22,
acute alcohol treatment. Finally, addi- DAVIS, C.C.; MELLENCAMP, M.; AND PREHEIM, 1992.
tional research is needed to delineate L. A model of pneumococcal pneumonia in
chronically intoxicated rats. Journal of Infec- SAAD, A.J.; DOMIATI-SAAD, R.; AND JERRELS, T.
some of the intracellular signaling Ethanol ingestion increases susceptibility of mice
tious Diseases 163:799–805, 1991.
events in immune cells that are affect- to Listeria monocytogenes. Alcoholism: Clinical
ed by acute and chronic alcohol use in DEVIERE, J.; CONTENT, J.; DENYS, C.; VANDEN- and Experimental Research 17:75–85, 1993.
order to better understand alcohol’s BUSSCHE, L.; SCHANDENE, J.; WYBRAN, E., AND
SPITZER, J., AND BAUTISTA, A. Alcohol, cy-
DUPONT, E. High IL-6 serum levels and in-
regulatory effects on the complex creased production by leukocytes in alcoholic
tokines and immunodeficiency. In: Friedman,
interactions of the immune system. H.; Klein, T.W.; and Specter, S., eds. Drugs of
liver cirrhosis. Correlation with IgA serum
Abuse, Immunity, and AIDS. New York: Ple-
levels and lymphokine production. Clinical and
num Press, 1993. pp. 159–164.
Experimental Immunology 77:221–225, 1989.
EDITORIAL NOTE FONG, I.W.; READ, S.; WAINBERG, M.A.; CHIA,
SZABO, G.; MANDREKAR, P.; AND CATALANO, D.
Inhibition of superantigen-induced T-cell
W.K.; AND MAJOR, C. Alcoholism and rapid proliferation and monocyte IL-1β, TNF and IL-
This article is accompanied by a progression to AIDS after seroconversion. 6 production by acute ethanol. Journal of Leuk-
“Suggested Reading” list that in- Clinics of Infectious Diseases 19:337–338, 1994. ocyte Biology 58:342–350, 1995.
cludes only key references. A com- GENTILELLO, L.M.; COBEAN, R.A.; WALKER, SZABO, G.; MANDREKAR, P.; VERMA, B.; AND
plete bibliography of sources A.P.; MOORE, E.E.; WERTZ, M.J.; AND CATALANO, D. Acute ethanol uptake prior to
consulted is available from the au- DELLINGER, E.P. Acute ethanol intoxication injury modulates monocyte TNFα production
thor. increases the risk of infections following pene- and mononuclear cell apoptosis. In: Faist, E., ed.
trating abdominal trauma. Journal of Trauma Immune Consequences of Trauma and Sepsis.
34:669–675, 1993. Berlin: Springer-Verlag, 1996. pp 252–260.
SUGGESTED READING JERRELS, T., AND SIBLEY, D. Effects of ethanol VICENTE-GUTIERREZ, M.M.; RUIZ, A.D.;
on T-cell-mediated immunity to infectious EXTREMERA, B.G.; GARCIA, J.M.B.; AND GEA,
ALDO-BENSON, M.; PRATT, L.; AND HARDWICK, agents. In: Friedman, H.; Klein, T.W.; and F.G. Low serum levels of alpha-interferon,
J. Alcohol can inhibit effect of IL-4 on activated Specter, S., eds. Drugs of Abuse, Immunity and gamma-interferon, and interleukin-2 in alcoholic
murine B cells. Immunology Research 11:117– Infections. Boca Raton: CRC Press, 1996. pp. cirrhosis. Digestive Disease Sciences 36:1209–
124, 1992. 129–141. 1212, 1991.
38 ALCOHOL HEALTH & RESEARCH WORLD
Alcohol and Compromised Immunity
ALCOHOL AND SUSCEPTIBILITY TO TUBERCULOSIS
Worldwide, tuberculosis (TB) is the leading cause of death Because alcohol use significantly inhibits cell-mediated
from a single infectious agent (Flynn and Bloom 1996). immunity, it compromises the body’s immune defense.
Mycobacterium tuberculosis, the agent responsible for TB, Thus, alcoholism—along with other diseases associated
is transmitted when a person inhales microscopic airborne with impaired cell-mediated immunity (e.g., HIV infec-
particles containing the organism (i.e., “droplet nuclei”) tion)—increases a person’s susceptibility to active TB
coughed up by someone with active TB disease, although infection as well as reactivation of latent disease (Flynn
prolonged exposure usually is necessary before an infec- and Bloom 1996). Researchers do not know, however,
tion becomes established. Initially M. tuberculosis attacks whether alcohol consumption itself or the liver damage and
the lung, where immune cells (i.e., macrophages and lym- malnutrition often associated with alcoholism are primarily
phocytes) battle the infection. In the absence of adequate responsible for the impaired immunity of alcoholics.
immunity, however, the bacteria ingested by macrophages Investigators studying mechanisms by which alcohol
continue to multiply within these immune cells, and char- predisposes people to TB recently have focused special
acteristic lesions called tubercles eventually form in the lungs. attention on the specific immune system components
Among other symptoms, people with active TB develop a participating in the body’s defense against M. tuberculosis
bloody cough, fatigue, and difficulty breathing. TB can and related mycobacteria. Alcohol use has been found to
affect any organ system or develop into systemic infection hinder the body’s antimycobacterial defense on multiple
(i.e., miliary TB) when infected cells spread from the lungs levels, including through impaired macrophage response,
and disseminate through the bloodstream. No effective altered levels of the proteins that act as intercellular medi-
vaccination against TB currently exists, but 6 to 9 months ators (i.e., cytokines), and a disturbed balance between the
of treatment with multiple antituberculous drugs will cure two basic types of acquired immunity: cell-mediated im-
most TB patients who complete the course of therapy. munity and immunity provided by circulating antibodies
Sociological studies show that TB is more prevalent in (i.e., humoral immunity). Each of these interrelated conse-
low-income, densely populated housing areas—settings quences is discussed in the sections that follow.
often associated with high rates of alcoholism.1
Numerous studies also have noted a direct association Impaired Macrophage Response. Macrophage activation
between alcoholism and pulmonary tuberculosis is considered essential for local containment and destruc-
(Jacobson 1992). Such apparent susceptibility to TB tion of mycobacteria (including M. tuberculosis) and
infection among alcoholics, especially those who are other invasive microorganisms. Thus, macrophage activi-
homeless or indigent, can be attributed both to biological ty is the hallmark of resistance to TB (Flynn and Bloom
and to social and behavioral factors. 1996). These immune system cells (along with the mono-
cytes that give rise to them) play a key role in directly
Biological Factors “presenting” the chemical identifiers that stimulate an
Although approximately one-third of the world’s popula- immune response (i.e., the antigens) to lymphocytes in
tion is infected with M. tuberculosis, only about 10 percent the body’s lymph tissue. In response to antigen presenta-
will experience either acute or reactivated disease (Flynn tion, certain lymphocytes (i.e., T lymphocytes) develop
and Bloom 1996). Clearly, the body’s immune system is into T cells that specifically target the M. tuberculosis
quite capable of controlling M. tuberculosis in most cases. organism for destruction. These T cells rapidly multiply
Any illness or condition associated with an impaired im- and circulate throughout the body. Evidence from several
mune system, however, can increase the likelihood of laboratories suggests that activation of two types of T
developing active TB. In particular, numerous animal cells in particular (i.e., CD4 and CD8 T cells) is impor-
studies have confirmed that the body’s control of M. tuber- tant in the control of mycobacterial infection (Flynn et al.
culosis infection resides in its ability to mobilize macro- 1992; Kaufmann and Flesch 1986; Leveton et al. 1989;
phages and lymphocytes against invading organisms (i.e., Orme and Collins 1983, 1984; Flory et al. 1992).
cell-mediated immunity) (Dunlap and Briles 1993). Although alcohol likely affects many immune system
cells, macrophages and monocytes appear to be particularly
The terms “alcoholism” and “alcoholic” as used in this article are sensitive to its influences. Both acute and chronic alcohol use
summary terms for the diagnoses of alcohol abuse and alcoholism. may decrease the activation of antigen-specific T cells by
Compared with M. tuberculosis, MAC is a less invasive infectious inhibiting the macrophages’ capacity to present mycobacterial
agent, but it has been associated with both pulmonary and disseminated antigen to lymphocytes (Szabo et al. 1993). Bermudez and
disease in people with compromised immune systems (e.g., alcoholics Young (1991) have shown that alcohol also enhances the
or people with AIDS), just as TB has. The pathology and cell-mediated
immune mechanisms involved in the body’s defense against MAC are
survival of another pathogen (i.e., the Mycobacterium avium
similar to those seen in M. tuberculosis infection, making research on complex, or MAC2) within blood-derived macrophages in
this agent relevant to an understanding of TB control. people and liver macrophages (i.e., Kupffer cells) in mice.
VOL. 21, NO. 1, 1997 39
The same study demonstrated an increase in MAC colony 10). IL-12 enhances the activity of CD4 and CD8 T cells,
counts in the blood, liver, and spleen of alcohol-fed mice as well as natural killer cells, and triggers a cell-mediated
compared with controls, suggesting that alcohol use prior to immune response; elevated levels of IL-10, however,
and during MAC infection contributes to dissemination of inhibit production of IL-12 and other inflammatory cy-
the disease in the body. tokines. In recent studies of isolated human monocytes
In addition to decreasing the antimycobacterial activi- exposed to alcohol, researchers have observed elevated
ty of macrophages, alcohol consumption also reduces IL-10 levels, inhibition of IL-12, increased production of
macrophage response to immune system modifiers. For other mediators that check the immune system (e.g.,
example, the cytokines known as tumor necrosis factor transforming growth factor beta [TGF-β]), and a reduced
alpha (TNF-α) and granulocyte-macrophage colony- antigen-presenting capacity (Szabo et al. 1993, 1996;
stimulating factor (GM-CSF) both have been shown to Mandrekar et al. 1996). All of these effects imply that
induce macrophages to inhibit the growth of and destroy acute alcohol consumption impairs a cell-mediated (i.e.,
mycobacteria. In vitro studies suggest that alcohol im- Th1-type) immune response and consequently tilts the
pedes the protective effect exerted by these cytokines, balance of the immune system toward humoral (i.e., Th2-
however (Bermudez and Young 1991). type) immune functions. Given the importance of cell-
mediated immunity in overcoming TB infection, the
Altered Cytokine Levels. TNF-α, one of the inflammatory implications of this shift can be significant for alcoholics
mediators derived primarily from macrophages, plays a exposed to M. tuberculosis.
major role in antimycobacterial defense (Nelson et al. 1995; Researchers also have found, however, that the cy-
Flynn and Bloom 1996). This cytokine directly inhibits tokine gamma-interferon (IFN-γ) plays a critical role in
mycobacterial growth in vitro, recruits additional inflamma- determining whether a Th1- or Th2-type response will
tory cells, and induces the action of other antimycobacterial dominate in alcohol-exposed monocytes. Recent studies
mediators (e.g., nitric oxide and reactive oxygen radicals). showed that the presence of IFN-γ decreased alcohol-
One of the most dramatic effects of both acute and induced IL-10 production, thus canceling IL-10’s inhibi-
chronic alcohol use is the impaired capacity of monocytes tion of IL-12 and thereby augmenting cell-mediated (i.e.,
to produce cytokines that trigger inflammation, particularly Th1-type) immunity (Mandrekar et al. 1996; Szabo et al.
TNF-α, in response to bacterial or mycobacterial infection. 1996). This finding supports the demonstration by Flynn
In a study with rats, Nelson and colleagues (1989) found and Bloom (1996) that IFN-γ is essential to resistance
that the immune cells first to be exposed to mycobacteria against TB in mice. Vicente-Gutierrez and colleagues
(i.e., macrophages in the alveoli of the lungs) showed a (1991) have reported decreased IFN-γ in chronic alco-
reduced capacity to manufacture TNF-α following both holics, indicating that suppressed IFN-γ levels in alco-
chronic and acute alcohol consumption, an effect that holics likely contribute to an impaired cell-mediated
likely would contribute to a compromised immune defense immune response during mycobacterial infection.
against TB. Of interest, Denis (1991) found that TNF-α Taken together, both acute and chronic alcohol use
had a beneficial effect on survival when it was infused into have been shown to predispose the body to compromised
mice inoculated with M. tuberculosis, suggesting that defense against mycobacteria. Although researchers still
alcohol’s negative effect on the antimycobacterial activity need to refine our understanding of the exact mechanisms
of macrophages potentially could be overcome. by which alcohol use decreases antimycobacterial defense,
the immunosuppressive effects of alcohol on monocyte and
Disturbed Cell-Mediated and Humoral Immunity Bal- macrophage function, cytokine production, and antigen-
ance. Both acute and chronic alcohol use are associated specific T-cell activation appear to be key factors in the
with a shift toward the predominance of humoral immune increased susceptibility to TB following alcohol use.
functions at the expense of cell-mediated functions, as
indicated by increased levels of circulating antibodies and Social and Behavioral Factors
decreased T-cell activity. Specifically, acute and chronic For alcoholics, especially those who are indigent or
alcohol use alter the profile of the T-cell population so homeless, several social and behavioral factors converge
that the type of cells known as T-helper-2 (Th2), which to increase their vulnerability to TB and to hinder their
are associated with humoral immunity, dominate over recovery from the disease.
those known as T-helper-1 (Th1), which are associated
with cell-mediated immunity. One recent hypothesis High-Risk Living Conditions. Typically, indigent and
suggests that this shift comes about through alcohol’s homeless alcoholics dwell in crowded and impoverished
effects on monocytes. Monocytes play a pivotal role in living conditions. Such an environment significantly in-
supporting a Th1 immune response in two ways: through creases their chances for repeatedly inhaling M. tuberculo-
their capacity to present antigen to activate T cells and sis droplet nuclei. With prolonged exposure, a person is
through their manufacture of the important cytokines more likely to acquire an active TB infection and subse-
known as interleukin-12 (IL-12) and interleukin-10 (IL- quently spread the disease by coughing up more infectious
40 ALCOHOL HEALTH & RESEARCH WORLD
Alcohol and Compromised Immunity
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