chemical mediators, robbins, inflammation, cytokines, tissue necrotic factor, interleukins vasoactive amines, arachdonic acid, prostaglandins, lipoxins

1. Mediators of
inflammation
Dr Sehrish Ahmed

2. Overview
• General Properties
• Types of mediators
• Clinical aspects

3. What are
they???
Mediators of inflammation are the substances that
INITIATE & REGULATE the inflammatory reactions

4. What
stimulates
the
production
of
mediators?
Microbial
products
Necrotic
debris

5. Properties
• Specific stimulus
• Short lived
• Cascade reaction

8. Histamine
heat, cold,
irradiation,
trauma
C3a & C5a:
Anaphylatoxins
IL-1 & IL8.

10. Serotonin
 5- Hydroxytryptamine
 Action similar to histamine

11. Newly
formed
Cell
derived
Mediators
Arachidonic
acid
metabolites
Platelet
Activating
Factor
Neuropeptides Chemokines
Nitric oxide Cytokines

12. Arachidonic Acid
Ca
Activation of
Phospholipase A2Free AA

13. Free Arachidonic
Acid
Eicosanoids
Thromboxane, prostaglandins,
leukotrienes & Lipoxins

14. LEUKOTRIENES
Leukocytes
and
mast cells
More potent than Histamine
PROSTAGLANDINS
Mast cells,
macrophages,
endothelial cells
LIPOXINS

15. Systemic Manifestations of
Inflammation
prostaglandins are involved in the
pathogenesis of pain and fever
PGE2 makes the skin hypersensitive to
painful stimuli, and causes fever
during infections

16. What did we understand so far??
The metabolites of arachidonic acid i.e PG, LT and
Lipoxins mediates
– Vasodilation
– Vasoconstriction
– Bronchodilation
– Bronchoconstriction
– Platelet aggregation and inhibition
– Chemoattraction
– Inhibition of chemotaxis
CAN MEDIATE
POSSIBLY EVERY
STEP OF
INFLAMMATION

17. Cox1 &
Cox2
Inhibitors
Zileuton
Steroids
Leukotrien
es
Receptor
Antagonist

18. CYTOKINES

19. OTHER NAMES
• INTERLEUKINS
• LYMPHOKINES
• INTERFERONS
• CHEMOKINES
• MONOKINES

20. INTERLEUKINS
• Mediate the
leukocyte cross-
talk
• Upto 38 ILs have
been identified

21. Significant role
in Acute
inflammation:
• IL 1
• IL 6
• IL 17
• TNF Alpha
• Chemokines

22. Sources of most of cytokines are
MACROPHAGES T LYMPHOCYTES
IL-1
IL-6
TNF-Alpha
IL-17
TNF-Beta

23. LOCAL INFLAMMATION
SYSTEMIC PROTECTIVE EFFECT
SYSTEMIC PATHOLIGICAL
EFFECT

24. TNF antagonists have been remarkably
effective in the treatment of chronic
inflammatory diseases,
• rheumatoid arthritis,
• psoriasis,
• inflammatory bowel disease

25. CHEMOKINES
(Macrophages & Endothelial cells)
a family of small (8–10 kD) proteins that act primarily as chemo-attractants
for specific types of leukocytes
• 4 types

26. C
Chemokine
Lymphocytes
CC
Chemokines
Monocyte, Eosinophils
CXC
Chemokine
Neutrophils
CX3C
Chemokine
Monocytes and T cells
(Both chemoattractant
and adhesion
molecule)

27. FUNCTIONS
In Acute
Inflammation
Maintenance
of tissue
Architecture

28. Role of other cytokines

29. PLASMA DERIEVED

30. Complement System

34. Kinins

35. • Histamine, ProstaglandinsVasodilation
• Histamine, C3a and C5a,
Leukotrienes C4, D4, E4
Increased vascular
permeability
• TNF, IL-1, Chemokines, C3a, C5a,
Leukotriene B4
Chemotaxis, leukocyte
recruitment and
activation.
• IL-1, TNF, ProstaglandinsFever
• Prostaglandins, BradykininPain

36. Thankyou!