The document discusses various chemical mediators of inflammation, including vasoactive amines (histamine and serotonin), arachidonic acid metabolites, lysosomal components, platelet activating factor, cytokines, nitric oxide, and plasma proteases. It details their sources, actions, and roles in processes such as vasodilation, increased vascular permeability, chemotaxis, and immune response. Additionally, it outlines the interlinked systems involved in inflammation, including the kinin, clotting, fibrinolytic, and complement systems.

1. Chemical Mediators of
Inflammation
 These are a large and heterogenous
group of endogenous compounds that
increase vascular permeability.
 Other actions include vasodilation,
chemotaxis, fever, pain and tissue
damage.

3. Vasoactive amines
 These are 2 substances Histamine and
Serotonin which play an early role – first 1hr.
 Histamine – is stored in mast cells, basophils
and platelets.
 Released by various stimuli such as heat, cold,
radiation, trauma, chemicals, Ag-Ab Rx., C3a,
C5a, IL, Substance P etc.
 Main actions are VD, ^ V.P, pain and itching

4. Vasoactive amines
 Serotonin – 5HT. – Present in tissues such as
chromaffin cells of GIT, spleen, nervous system,
mast cells and platelets.
 Actions are similar as Histamine but less
pronounced.

5. Arachidonic Acid (AA)
metabolites
 AA is a fatty acid called eicosa-tetra-enoic
acid (ETE)
 Its sources are from the diet and from
conversion of linoleic acid to AA.
 AA must first be activated by C5a to form
its metabolites
 AA metabolites are formed by 2 pathways

6. Arachidonic Acid (AA)
metabolites
 AA metabolites are formed by 2 pathways
1. Cyclo-oxygenase pathway
( Prostaglandins, ThromboxaneA2, Prostacyclin)
2. Lipo-oxygenase pathway
( Leukotrienes or Slow reacting substances (SRS)

7. Cyclo-oxygenase pathway

8. Lipo-oxygenase pathway

9. Lysosomal components
 These are substances released by neutrophils and
monocytes
 Neutrophils – Azurophilic granules release MPO, acid
hydrolases, elastase, collagenase and protease
 Neutrophils - Specific granules contain lactoferrin,
lysozyme, alkaline phosphatase and collagenase
 Monocytes – acid proteases, collagenase, elastase and
plasminogen activator

10. Platelet activating factor (PAF)
 Released from IgE sensitised basophils or
mast cells, other leucocytes, endothelium
and platelets.
 Actions are Platelet aggregation, release
reaction, ^ V.P, VD, B.C, leucocyte
adhesion, chemotaxis

11. Cytokines
 These are polypeptide substances produced by
activated lymphocytes (lymphokines) and monocytes
(monokines).
 They may act on itself or other cells
 Main cytokines are IL-1, TNF-a and TNF-b, IF-g, and
chemokines IL-8, PF-4.
 IL-1 and TNF-a – produced by activated macrophages
 TNF-b, IF-g – activated T cells
 Chemokines – IL-8 (macrophages), PF-4 (platelets)

12. Actions of Cytokines
 IL-1 & TNF-a, TNF-b - ^ leucocyte adherence,
thrombogenecity, secretion of other cytokines,
acute phase reactions
 IF-g – causes activation of macrophages &
neutrophils, synthesis of NO synthase
 Chemokines act as chemotactic factors for
neutrophils ( IL-8), monocytes ( PF-4, MCP-1),
eosinophils (eotaxin)

13. Nitric Oxide
 Liberated by endothelial cells
 Causes VD, anti-platelet activation,
microbicidal action.

14. PLASMA PROTEASES
 These are substances derived from 4
systems
The kinin system
The clotting system
The fibrinolytic system
The complement system

15. PLASMA PROTEASES
 These are products derived from
activation of 4 interlinked systems
The kinin system
The clotting system
The fibrinolytic system
The complement system
The key role is played by the Hageman Factor
(Factor XII)

16. 4 interlinked systems

17. The kinin system

18. The kinin system
 Effects of Bradykinin
 Smooth muscle contraction
 Vasodilation
 Increased Vascular Permeability
 Pain

19. The Clotting System

20. The Clotting System
 Actions of Fibrinopeptides
 Increased Vascular permeability
 Chemotaxis
 Anticoagulant activity

21. The Fibrinolytic System

22. The Fibrinolytic system
 The actions of Plasmin are
 Activation of Factor XII
 Splits off C3 to form C3a which is an opsonin
 Degrades fibrin to form fibrin split products
(FDP) which ^ V.P and chemotaxis

23. The Complement System
 Activation of this system can occur by 2 pathways
 Classic Pathway (Ag-Ab reactions)
 Alternate Pathway (Bacterial toxins, cobra venom)
The end products by either of these pathways are
anaphylatoxins (C3a, C4a, C5a) and Membrane attack
complex (MAC).
Actions of anaphylatoxins are
 release of histamine from mast cells and basophils
 increased vascular permeability
 phagocytosis (C3b)
 Chemotaxis (C5a)
 Cell membrane damage (MAC)