Inflammation is the body's normal response to injury and involves four key signs: redness, swelling, heat, and pain. The inflammatory response involves increased white blood cell count, release of inflammatory substances, and fever. Inflammation can be either acute (short-term) or chronic (long-term). Chronic inflammation involves lymphocytes and plasma cells and is associated with diseases like arthritis and cancer. Cancer and inflammation are linked, as reactive oxygen species generated during inflammation can damage DNA and the inflammatory microenvironment provides survival signals that can promote tumor growth and progression.

1. Inflammation
Jayanta Saha
MSc

2.  What is inflammation?
A normal response of living tissues
to injury. It prepares the tissue for
healing and repair.
Ultimate goal is to replace injured
tissue

3. The four principal effects of inflammation
 rubor,
 tumor,
 calor and
 dolor
Those were described nearly 2,000 years ago by the
Roman Aulus Cornelius Celsus, more commonly
known as Celsus.

4. Redness (rubor)
An acutely inflamed tissue appears red, due to
dilatation of small blood vessels within the
damaged area (hyperemia).
Swelling (tumor)
Swelling results from edema, the accumulation
of fluid in the extravascular space as part of the
inflammatory fluid.

5. Heat (calor) Increase in temperature is readily
detected in the skin. It is due to increased
blood flow (hyperemia) through the region,
resulting in vascular dilation and the delivery of
warm blood to the area.
Pain (dolor) Pain results partly from the
stretching and distortion of tissues due to
inflammatory edema.
Rubor, Tumor, Calor and Dolor

6. Loss of function (functio laesa) Loss of function, a well-
known consequence of inflammation, was added by Virchow
(1821-1902) to the list of features described in Celsus’ written
work.
Rubor, Tumor, Calor and Dolor

8. Inflammatory Response
 Leukocytosis
 White blood cell count increased
above the normal range
 It is not a disorder or a disease, but
a sign of illness.
 IL-1 and TNF reach the bone
marrow and cause accelerated
release of leucocytes into the
circulation

9. Inflammatory Response
 Endotoxemia
 Bacteria enter blood stream & release
endotoxin
 WBC react to the presence of bacteria
and release inflammatory substance-
excessive cytokine production
 Endotoxemia specifically refers to
circulating gram-negative bacterial toxic
products (LPS).
 There are some cell wall products
released from gram-positive bacteria that
can have a similar toxic effect.

10. Fever
Fever is a common systemic response to inflammation
The elevation of body temperature is thought to improve
the efficiency of leukocyte killing and may also impair the
replication of many invading organisms.
.
Inflammatory Response

11. Type of Inflammation
Inflammation is divided into Acute and Chronic type…..
Acute inflammation: The inflammation process which starts
immediately is called acute inflammation.
Cardinal Signs of acute inflammation
• Redness (rubor)
• Swelling (tumor)
• Heat (calor)
• Pain (dolor)
• Loss of function (functio laesa)

12. Components of acute and chronic inflammation
PAMP tissue
serotonin,

13. Acute inflammation
• Main components:
–Vascular changes
• Vasodilation
• Vascular permeability
• Increased adhesion of
white blood cells
– Cellular events
• Cellular recruitment
and activation of
neutrophils
(polymorphonuclear
leukocytes)

14. Acute inflammation
1. Vasodilation:
- The reactions of blood vessels
- Alterations in vascular caliber (diameter)
- Causes decrease in blood pressure
2. Vascular leakage and edema:
- The accumulation of fluid and proteins of plasma in the
extravascular tissues (interstitium)
3. Leukocyte emigration to extravascular tissues
A. Margination and rolling
B. Activation and adhesion
C. Transmigration

15. Acute inflammation
1. Vasodilation:
• Change in vessel flow
– NO, histamineèvascular smooth muscleè
vasodilationèincreased blood flow (heat & redness)
– Stasis: slowed blood flow, hyperviscosity
– Margination of circulating leukocytes & endothelial
activation
• Followed by increased permeability of the
vasculature
– Formation of an early transudate (protein-poor filtrate
of plasma) gives way to exudate (protein-rich filtrate)
into extracellular tissues

18. 3. Leukocyte emigration

19. Features of chronic inflammation
• Chronic inflammation = long duration
• Components:
– Lymphocyte, plasma cell, macrophage (mononuclear
cell) infiltration

20. Acute vs. Chronic inflammation

21. Diseases with chronic Inflammation

22. Inflammation and Cancer: A Comparative View, J Vet Intern Med 2012;26:18–31, Wallace B. Morrison
The normal end result of inflammation is that any damaged tissue or
damaged DNA is repaired, the inflammatory response is quenched,
and healing takes place. However, during active inflammation the
cellular microenvironment is highly reactive and unstable attributable
to the combined effects of the many and abundant reactive oxygen
and nitrogen species, cytokines, chemokines, reactive aldehydes,
and growth factors that are present.

23. Most of the literature agrees that the sustained
generation of free radicals such as the reactive
oxygen species
 hydroxyl radical (OH·) and superoxide (O2·)
and the
reactive nitrogen species
 nitric oxide (NO·) and peroxynitrite (ONOO·)
1.Reactive Oxygen and Nitrogen Species
Inflammation and Cancer: A Comparative View, J Vet Intern Med 2012;26:18–31, Wallace B. Morrison

24. 2.Macrophages
 Macrophages in particular are important tumor infiltrating
cells that affect tumor growth and metastasis.
 They are found in 2 different polarization states known as
M1 and M2.
 M1 macrophages produce interleukin 12 and promote
tumoricidal responses,
 The mechanisms governing macrophage polarization are
unclear.
Another inducible enzyme with carcinogenic properties that
 is active within inflamed and malignant tissues is
cyclooxygenase-2 (COX-2).
Inflammation and Cancer: A Comparative View, J Vet Intern Med 2012;26:18–31, Wallace B. Morrison

25.  The mechanism by which inflammation causes cancer can be modeled as
consisting of an intrinsic and extrinsic pathway.
 The intrinsic pathway is activated by oncogene activation and tumor suppressor
gene inactivation.
 An example of this is the inflammatory infiltrate noted in human breast cancer
described by Virchow in 1863.
 The extrinsic pathway is one of inflammation that increases the risk of cancer at
certain anatomical sites such as the colon, pancreas, prostate.
 Many of the signaling pathways involved in inflammation and normal healing also
play a dual role in providing survival and proliferative signals to initiated cells that
lead to cancer promotion and progression.
 The Mitogen Activated Protein Kinase (MAPK) pathway also has a well-recognized
dual role in cancer development and in inflammation.
Inflammation and Cancer: A Comparative View, J Vet Intern Med 2012;26:18–31, Wallace B. Morrison

26. MAPK pathway