1) Evidence suggests prostaglandins play a role in asthma pathogenesis by causing inflammation in the lungs. Low prostaglandin E levels are found in asthmatic patients during attacks. 2) Prostaglandins can influence the adenyl cyclase-cyclic AMP system and histamine release from cells. A drop in prostaglandin E makes the lungs more sensitive to stimuli by reducing this inhibitory effect. 3) Studies found higher plasma levels of prostaglandin F2α and lower levels of prostaglandin E in asthmatic patients, providing evidence prostaglandins cause asthma. Corticosteroids may exert their beneficial effect through influence on the prostaglandin system

1. Role of different prostaglandins
in asthma
Name:eman abd elraouf ahmed
youssif
Immunology department

2. The content
Evidence that prostaglandins cause inflammation
Mechanism of action
conclusions
references

3. introduction
Bronchial asthma is a disease characterised by an increased
responsiveness of the trachea and bronchi to various stimuli,
associated with reversible narrowing of the airways. A rise in
immunoglobulin E (IgE) can be demonstrated in individuals who
develop an attack of asthma on exposure to an allergen. Histamine,
SRS-A and kinins from the basophils and mast cells which are
abundant in the ungs, are liberated as a result of reaction
between allergen and cell fixed lgE.But in some individuals
it is not possib e to detect the specific allergen and increased

4. IgE levels in the plasma, indicating that IgE may not be the sole
mediator of asthma. Further, adrenergic drugs, which are commonly
used in asthma, are known to enhance cellular cyclic AMP levels and
thus may inhibit or block the release of histamine, SRS-A and Kinins.
However, adrenergic drugs are not always helpful in asthma. The
beta-adrenergic theorproposes that in asthmatics there is a partial
blockade of beta-receptors of the sympathetic nervous system through
which the beta-adrenergic drugs are known to act .

5. But this
theory does not explain why individuals who are not allergic to
analgesics develop an attack of asthma on exposure to analgesics
1 ike aspirin, indomethacin etc., which are known to have no effect
on beta-receptors .This shows that other mechanisms may be
playing an important role in the pathogenesis of asthma. Our
recent finding that prostaglandin E(PGE) levels are low in bronchial
asthmatics during an attack ,including those in whom the attack
id due to the ingestion of analgesics shows that possibly the
prostaglandin system is involved in the pathogenesis of asthma.

6. Steroids, Analgesics, sympathetic nervous system and PGs
It is well known that PGE’s (PGEl and PGEP) are potent
bronchodilators invivo and in vitro. whereas PGF compounds are
broncho constrictor in nature(b) Prostaglandins are also known
to influence the adenylcyclase-cyclic AMP system of various types
of cells .Corticosteroids, which are employed in the treatment
of asthma are also known to modify the PG system .Treatment
of rats with PGEl and PGE2 suppresses antigen induced release of
SRS-A, which is mediated by IgE antibody .Thus it is likely
that prostaglandins have anti-allergic activity. Further, persons
who show idiosyncrasy to aspirin -like drugs is not of immunologic
type but has been shown to be due to the suppression of PG
generation in tissues of the patients .In addition PGs are
also known to regulate adrenaline and nor -’ adrenaline secretion
and thus may have a modulating effect on the beta-receptors
and the sympathetic system,

7. Prostaglandins in bronchial
asthma.
It is possible that an exposure to bronchospastic stimuli such as a
allergens, exercise or infection may produce a fall in the PGE
level
in the target cells of lungs (basophils and mast cells). This drop
in the PGE level may result in reduction in the activity of the
adenyl cyclase-cyclic AMP system, leading to the liberation of
histamine, SRS-A etc.from the target cells. This assumption is
strengthened by the observation that a fall in the PGE content of
mast cells leads to their degranulation .A fall in the levels
of the natural bronchodilator, PGE, may make the bronchial

8. Prostacyclin (PG12)
a newly discovered member of the PG family, is
knownto have vasodilator and bronchodilator properties .PG12
is considered as a circulating hormone being released from
lungs into the circulating blood with potent platelet antiaggregating
activity (t8,lg). PG12 is synthesized mainly by the
vessel walls of several species including man ,It enhances
platelet cyclic AMP levels probably by stimulating adenyl cyclase
activity .PC12 synthesis has been shown to be regulated by PGE2
in rat liver endothelial cells and presumably a similar regulatory
mechanism might be operating in the lungs also, Low doses of aspirin
selectively affect platelet cycle-oxygenase but less avidly the vessel
wall cycle-oxygenase system .Since analgesic induced asthma can
occur after the ingestion of a single tablet of aspirin (.325 mgm)
it can be asumed that PGE synthesis is inhibited (5) whereas PGI
synthesis may be less affected. As PGE can regulate PGl2 synthesis
a primary role for PGE and PGF is indicated in asthma though a
supportive role for PGl2 cannot be ruled out,

9. Evidence that prostaglandins cause
asthma

10. PLASMA PROSTAGLANDIN ACTIVITIES IN SOME
IMMUNO-INFLAMMATORY DISEASES
The role of prostaglandins (PGs) in the regulation of
immune and inflammatory responses has been investigated
by many workers (Bourne, 1974; Pelus and
Strausser, 1977).
The presence of increased PG activity in human
inflammation has been firmly established, and that
increased PG activity is a feature not only of the
integument, but also of deep tissue, is suggested by
the presence of PG activity in synovial fluid of
patients with rheumatoid arthritis (Ellattar, 1978).
Infectious processes and host defences against infection
have also been found to be connected with
dramatic changes in PG activities (Osheroff et al.,
1975; Plescia et al., 1975).

11. MATERIALS AND METHODS
A group of 30 asthmatic persons, ranging between
18-70yr, with spirometrically determined bronchospasm
were used. The forced expiratory volume in the first second
FEVI~ o showed values of less than 71~ in the whole group,
with an average of 50~; of these, 15 patients were free from
parasitic infestations and 15 were suffering from schistosomiasis
beside the bronchospasm. The schistosomal nature
of the condition was confined by positive urine and/or
positive stool examination for schistosomal ova. Both urine
and stool showed the presence of schistosomal ova, i.e. the
patients suffered from mixed schistosomiasis mansoni and
hematobium.
.

12. A group of 15 schistosomal patients of the same age
group but not suffering from bronchospasm, with FEV~
more than 80~o, were also examined.
A group of 15 clinically normal subjects were taken as
controls. The patients did not receive any treatment for at
least 15 days before the investigation was performed.
Peripheral venous blood was collected from all subjects in
the early morning for PG determination. Plasma was separated
from the freshly collected blood and PGs were extracted
according to the method of Unger et al. (1971). The
extracted PGs were estimated, using gas liquid chromatographic
methods according to Rosello and Gelpi
(1978). The statistical analysis of the results was done using
the Student's T-test according to Bailey (1959)

13. RESULTS
The plasma levels of PGF2~ and PGE in the
different groups investigated and the
statistical analysis
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14. Prostaglandins and asthma: The use of blood components for metabolic studies
The prostaglandins (PGs) are a class of naturally occurring acidic lipids
of highly potent biologic activities.l Of the three biologically important PGs,
PGFs and PGEs are actively metabolized in the lung2 whereas PGAs escape
degradation
by the lung. PGF,, is the major PG found in the lung of several
species, including man.3 PGF,, is a potent bronchoconstrictor in contrast to
PGE’s which relax tracheobranchial smooth muscle.4-7 Asthmatic individuals
have been shown to possess much higher sensitivity to the bronchoconstrictor
action
of PGF,, than nonasthmatic subjects. +I0 In addition, PGF,, has been shown
to be released from sensitized guinea pig lung following antigenic challenge,
where antigenic release of PGE has not been detected by specific
radioimmunoassay.”
Immunoglobulin E-mediated histamine release in vitro from human leukocytes
and lung fragments has been shown to be modified by PGE’s and
PGF’s.~~

15. MATERIALS AND METHODS
Leukocytes were suspended in
, Sigma Chemical Co., St. Louis, Missouri; 1.2 x 10-i M sodium chloride; 5.0 x 10-3 M
potassium chloride; 6.0 x 10-k M calcium chloride; 1.0 x 10-a M magnesium chloride; 0.03%
human serum albumin) and antigenic release and fluorometric assay of histamine were
performed according to a method slightly modified from the one described by May.14 The
final leukocyte counts ranged from 3 to 4 x lOa/ml.
The blood used for the assay of plasma and serum PGF was cooled in ice mater immediately
after being drawn from the central cubital vein. The plasma was obtained by
centrifuging heparinized blood at 1,200 g at a temperature between 0 and 4” C for 10 min.
Serum was separated from the cells by allowing the nonheparinized blood to coagulate, at
37” C for 30 min. All the samples were stored in silieonized glass or polystyrene tubes
below -20’ C prior to the assay. The group of patients studied consisted of equal number of
males and females 14 years of age or older. They had mild to no wheezing, no aspirin hypersensitivity,
and positive skin tests to environmental allergens. They intermittently had sympathomimetic
or xanthine drugs, but had no medication for 48 hr and no aspirin, indomethacin,
or steroids for 1 wk before the morning of blood collection. Healthy males and females
approximately in equal numbers, over 15 years of age without a history of allergy, were the
sources for the normal blood. PGF was measured by radioimmunoassay as described by
Caldwell and associates.15 Anti-PGF,, antibody was obtained commercially (Clinical Assays,
Inc., Cambridge, Mass.) as well as by immunizing rabbits .

16. RESULTS
Spontaneous PGF release
The cell suspensions were incubated at 37O C for up to 40 min. The suspensions
were cooled in ice water after varying periods of incubation. PGF released
during the incubation was measured with the supernatants obtained by centrifuging
the suspension at 150 g for 8 min at a temperature between 0 and 4’ C. The
cells of both nonasthmatic and asthmatic individuals were found to release PGF
Antigenic histamine release and release of PGF
Table I shows the effect of optimal antigenic challenge on PGF levels measured
in the supernatant after 40 min of incubation at 37“ C. The antigen was
used in concentrations identical to those in a separate series of experiments which
observed the release of more than 50% of cellular histamine. Except for one patient,
D. R., who had more than 10 times as much PGF release as control on antigenic
challenge, none of the patients showed a statistically significant difference .
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17. CONCLUSIONS
The concept presented here envisages that the levels of PGE and PGF are
balanced in the lungs (4,5,22) which contains the Complete system for
PG synthesis and metabolism (23) and that this balance is upset on
exposure to bronchospastic stimuli. Further it is hypothesized that
corticosteroids, which are used in the management of asthma, exert
their beneficial effect by virtue of their influence on the PG system
(8). Since PGE bypasses the beta-receptor in stimulating the adenyl
cyclase (24) the therapeutic potential for PGE in asthma should be
promising, in persons who are non responsive to beta-adrenergic drugs.
As PGs are known to be involved in mast cell degranulation (12) and
nor - adrenaline secretion (lo), possibly an interaction exists between
the histamanic, beta-adrenergic and PG receptors.

18. Mechanism of different
prostaglandins in asthma

31. references
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