This document summarizes different mediators of inflammation. It describes cell-derived mediators like vasoactive amines (histamine, serotonin), arachidonic acid metabolites from cyclooxygenase and lipoxygenase pathways, lysosomal components, platelet activating factor, cytokines, and nitric oxide. It also discusses plasma-derived mediators including the kinin system, clotting system, fibrinolytic system, and complement system. These mediators cause effects like vasodilation, increased vascular permeability, adhesion of leukocytes, and chemotaxis during inflammation.

1. Submitted by : Rafa Zubair NV
I M.Pharm
Pharmacology
Subject: Biochemical and
molecular pharmacology
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2. Mediators of inflammation
 Definition: Any messenger that acts on
blood vessels, inflammatory cells, or other
cells to contribute to an inflammatory
response.
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3. Classification
Cell derived mediators
Plasma derived mediators
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4. 4

5. 1. Cell derived mediators
a) vasoactive amines (serotonin,histamine)
b) arachidonic acid metabolites
 cycloxygenase pathway
 lipoxygenase pathway
c) Lysosomal components
d) Platelet activating factor
e) Cytokines (IL-1,TNF-α,TNF-β,IF-γ,Chemokines)
f) Nitric oxide and oxygen metabolites
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6. a) Vasoactive amines
Histamine :-
Stored in granuls of mast cells, basophiles and
platelets.
Released by the stimuli of various agents like Heat,
Cold, Irradiation, Irritant chemicals, Anaphilatoxins,
Interleukins,.. etc.
Actions ; Vasodilation
Vascular permeability
Itching and pain
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7. Serotonin/5-hydroxy tryptamine :-
Present in chromafin cells of GIT, Spleen, Nervous
tissue, Mast cells, Platelets.
Actions ; Similar to Histamine, but less potent
Vasodilation
Vascular permeability
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8. b) Arachidonic acid Metabolites
Lipoxygenase pathway Cyclo-oxygenase pathway
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9. c) Lysosomal comonents
Source :- Neutrophiles and monocytes
Potent mediators
Degredation of bacterial and extracellular components
Chemotaxis
Realease of acid proteases, collagenase, elastase,
plasminogen activator
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10. 10
d) Platelet activating factor
 Phospholipid derived mediator
 Released from :- Platelets, basophil, mast cells,
neutrophils macrophages, endothelial cells
 Actions :-
Vascular permeability
Vasoconstriction
Vasodilatation
Bronchoconstriction
Adhesion of leukocytes to endothelium
Chemotaxis, degranulation

11. e) Cytokines
“Cytokines are a diverse group of small protein
molecules with potent biological activity whose main
function is in the regulation of immune responses.”
Main Cytokines are :-
 Interleukins
 Interferons
 Tumor necrosis factor
 Chemokines
 Transforming growth factor-beta
 Adipokines- leptin & adiponectin
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12. Actions :-
 Adhesion of leucocytes to endothelium
 Synthesis of Prostacyclin, which is a vasodilator and
anti aggregator of platelets
 Synthesis of PAF and thrombogenic effect on
endothelial surface
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13. f) Nitric oxide and oxygen metabolites
 Endothelium derived relaxing factor
 Macrophages, endothelial cells, neurons
Actions :-
Vasodilation
Anti-platelet activating agent
Microbicidal action
 H2O2 , Superoxide, Toxic NO products produced by
activated neutrophiles and microphages
Actions :-
Endothelial cell damage, tissue damage and vascular
permeability
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14. 2.Plasma derived mediators
a) The kinin system
b) The clotting system
c) The fibrinolytic system
d) The complement system
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15.  4 interlinked systems
 Hageman factor(factor XII)
 End product of clotting ,fibrinolytic ,kinin system will
activate complement system.
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16. a) The kinin system
factor XII
contact
factor XIIa
prekallikrein activator
Plasma prekallikrein kallikrein
kininogen bradykinin
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17. Actions :-
Smooth muscle contraction
Vasodilation
 vascular permeability
pain
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18. b) Clotting system
factor XII
contact
factor XIIa
XI XIa +VIIa +PF3
X Xa +Va +PF3
prothrombin thrombin
fibrino fibrinogen fibrin
Peptides plasmin
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19. Actions :-
Increase vascular permeability
Chemotaxis for leucocytes
Anticoagulant activity
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20. C) Fibrinolytic system
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21. Actions :-
 Activation of factor XII to form prekallikrein activator
that stimulates kinin system to generate bradykinin
 Splits off complement c3 to form c3a,which is
permeability factor
 Degrades fibrin to split products, they increase
vascular permeability
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22. D) Complement system
 Product of complement system is anaphylatoxins c3a
and c5a.
 Potency is c3a>c5a>c4a
 Actions:- release histamine from mast cells and
basophils
 C5a is chemotactic for leucocytes.
 Membrane attack complex cause pores in cell of
invading microbes.
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