This document discusses mediators of inflammation, which are substances that initiate and regulate the inflammatory reaction. There are several types of mediators, including vasoactive amines like histamine and serotonin, arachidonic acid metabolites called eicosanoids, and cytokines. Eicosanoids are potent mediators that are derived from arachidonic acid through either the cyclooxygenase pathway, producing prostaglandins, thromboxanes, and prostacyclin, or the lipoxygenase pathway, producing leukotrienes. These mediators have various effects like vasodilation, vasoconstriction, and bronchodilation or bronchonconstriction.

1. MEDIATORS OF INFLAMMATION
Dr. D. VAMSHIKRISHNA, M.D (H)

2. Learning Objectives
1. What are Mediators of Inflammation?
2. What are the General Properties of
Mediators of Inflammation?
3. What are the Different Types of
Mediators?

3. Mediators of Inflammation.
• These are the Substances which
INITIATE REGULATE
INFLAMMATORY REACTION

4. General Properties of Mediators of
Inflammation.
1. Mediators can be:
CELL- DERIVED PLASMA DERIVED
PREFORMED/
READYMADE
(stored in the
Granules)
DE-NOVO
(FORMED NEWLY)
Synthesized if needed

5. 2. Produced only in response to agents that
stimulate inflammation.
3. Can stimulate the release of another mediator.
4. Short Life-Span- Rapidly removed from
circulation
5. Can act on Wide-variety of Cells.

6. Different Types Of Mediators.
CELL- DERIVED PLASMA DERIVED
PREFORMED/
READYMADE
(stored in the
Granules)
DE-NOVO
(FORMED NEWLY)
Synthesized if needed
VASOACTIVE
AMINES
•HISTAMINE
•SEROTONIN
•ARACHIDONIC ACID
METABOLITES
(EICOSANOIDS)
•LYSOSOMAL
COMPONENTS
•CHEMOKINES
•CYTOKINES
PRODUCTS OF:
1. THE KININ SYSTEM
2. THE CLOTTING
SYSTEM
3. THE FIBRINOLYTIC
SYSTEM
4. THE COMPLEMENT
SYSTEM

7. VASOACTIVE AMINES
• First mediators to be released during
inflammation.
• Derived from amino acid- HISTIDINE
• They are Histamine and Serotonin

8. Histamine
Sources:
• Mast cells (Most imp)
• Basophils
• Platelets

9. Stimuli for release of Histamine:
• Heat, Cold, Irradiation, Trauma, Irritant
Chemicals, Immunologic Reactions.
• C3a, C5a- Anphylatoxins.
• Interleukins- IL-1, IL-8

10. Actions of Histamine:
• Increase in Vascular Permeability.
• Vasodilatation.
• Itching and Pain
• Responsible for Flare and Wheal reaction of
Skin.

11. Serotonin/5-Hydroxytryptamine
Sources:
• Mast cells
• Platelets
Also:
• Chromaffin cells of GIT, Spleen, Nervous
tissue

12. Actions of Serotonin:
• The actions of 5-HT are similar to histamine
but it is a less potent mediator of increased
vascular permeability and vasodilatation than
histamine.

13. 2. ARACHIDONIC ACID METABOLITES
(EICOSANOIDS):
• Arachidonic acid metabolites or eicosanoids
are the most potent mediators of inflammation,
much more than oxygen free radicals.
Eicosanoids:
- Prostaglandins (D2, E2, F2-α, I2)
- Thromboxane
- Leukotrienes
- Lipoxins

14. Source: Tissue injury
Damage to Mast cells, Endothelial cells, Macrophages, Platelets
Ca++ Influx into cells
ACTIVATION OF PHOSPHOLIPASES
ARACHIDONIC ACID
(PRESENT IN CELL MEMBRANE)
FREE ARACHIDONIC ACID
ARACHIDONIC ACID METABOLITES
OR EICOSANOIDS
1. Cyclo-oxygenase
Pathway
2. Lipooxygenase
Pathway

15. Cyclo-OXygenase Pathway (COX PATHWAY)
Cyclo-oxygenase COX-1 and COX-2,
ACTIVATED ARACHIDONIC ACID
PROSTAGLANDIN ENDOPEROXIDE (PGG2).
PGH2
PGD2 PGE2 PGF2-α Prostacyclin (PGI2) Thromboxane A2 (TXA2)

16. Action of COX Pathway Eicosanoids:
PGD2 PGE2 PGF2-α Prostacyclin (PGI2) Thromboxane A2 (TXA2)
VASODILATATION
VASOCONSTRICTION
NORMAL BLOOD VESSEL
1. VASODILATATION
2. VASOCONSTRICTION

17. PGD2 PGE2 Prostacyclin (PGI2)
3. BRONCHODILATION
BRONCHODILATORS

18. PGF2-α
Thromboxane A2 (TXA2)
4. BRONCHOCONSTRICTION
BRONCHOCONSTRICTORS

19. Lipo-Oxygenase Pathway:
Lipo-oxygenase ( a Neutrophil Enzyme)
ACTIVATED ARACHIDONIC ACID
HYDROPEROXY EICOSATETRAENOIC ACID (5-HPETE)
(Peroxidation)
LEUCOTRINE A4
LEUCOTRINE B4 LEUCOTRINE C4
LEUCOTRINE D4
LEUCOTRINE E4
LIPOXINS

20. Action of Lipo-Oxygenase Pathway Eicosanoids:
LEUCOTRINE B4
1. CHEMOTAXIS

21. LEUCOTRINE C4
LEUCOTRINE D4
LEUCOTRINE E4
LIPOXINS
VASODILATATIONVASOCONSTRICTION
2. VASODILATATION
3. VASOCONSTRICTION

22. LEUCOTRINE C4
LEUCOTRINE D4
LEUCOTRINE E4
LIPOXINS
BRONCHOCONSTRICTORS
4. BRONCHOCONSTRICTION