Chemical mediators of inflammation - B. Pharma 2nd Semester Pathophysiology notes pdf

Chemical mediators of inflammation


       Chemical mediators of inflammation

       Cell derived mediators

       Plasma derived mediators


At the end of this lecture, student will be able to

         List various chemical mediators of inflammation

         Describe the  formation and functions of cell derived mediators

        Describe the formation and functions of plasma derived mediators

Chemical mediators of inflammation

       Endogenous compounds

       Released during inflammation

       Increases vascular permeability

       Edema, Destruction of inflammatory agents

Cell derived mediators of inflammation

       Vasoactive amines – Histamine, Serotonin, Neuropeptides

       Arachidonic acid metabolites

      Via COX pathway - Prostaglandins, Thromboxane A2, prostacyclin

      Via LOX pathway - 5-HETE, leukotrienes

       Lysosomal system

       Platelet activating factor

       Nitric oxide and oxygen metabolites

Plasma derived mediators of inflammation

       The kinin system

       The clotting system

       The fibrinolytic system

       The complement system

Vasoactive amines (Autocoids)

Amine autocoids


       5 – HT / Serotonin

Released within 1 hour of inflammatory response


       Stored in mast cells, basophills & platelets

Released due to – Heat/cold radiations

      Chemical irritant & immunological reactions

      Anaphyla toxins

Main actions of Histamine

       Vaso dilation

       ↑ permeability of venules

       Itching & pain

       Release of other cell derived mediators

       Broncho constriction


       Present in chromaffin cells of GIT

       In spleen, nervous system, mast cells & platelets



       ↑vascular permeability

       Less potent than histamine


       Tachykinin neuropeptides - substance P, neurokinin A, vasoactive intestinal polypeptide (VIP) & somatostatin

       Produced in the central and peripheral nervous systems


       Increased vascular permeability

       Transmission of pain stimuli

       Mast cell degranulation

Arachdonic acid Metabolite

       Tissue injury – Phospholipase A2 activation

       Conversion of phospholipids into arachdonic acid 

Metabolism of arachdonic acid follows 2 pathway

       COX (Cyclo-oxygenase) – Pathway

       LOX (Lipo- oxygenase) – Pathway

COX Pathway

LOX Pathway

Lysosomal components

Granules of Neutrophills

Primary granules 

·         Myeloperoxidase

·         Acid hydrolase

·         Neutral proteases

Secondary granules

·         Lactoferrin

·         Lysozyme

·         Alkaline phosphatase

·         Collagenase

Granules of Monocytes & Tissue macrophages

       Cells on degranulation releases mediators like

       Acid proteases



       Plasminogen activator

More involved in chronic inflammation

Platelet Activating Factor (PAF)

IgE-sensitised basophils or mast cells, other leucocytes, endothelium and platelets

       ↑ vascular permeability

       Vasodilatation in low concentration and vasoconstriction

       Broncho constriction

       Adhesion of leucocytes to endothelium



       Group of polypeptide substances

       Produced by activated lymphocytes/ monocytes

       Interleukin 1 & 8

       Tumor necrosis factor


       Platelet factor


       IL –I, TNF α & β - ↑ leucocyte adherence, Platelet aggregation, proliferation of fibroblast

       Interferon gamma – activation of macrophages & neutrophils

       IL-8 – Chemotactic of neutrophills

       PF – 4 – Chemotactic for neutrophills, monocytes & eosinophills

Nitric oxide & oxygen metabolites

       Released by activated macrophages from vascular endothelium


       Inhibiton of platelet aggregation

       Killing of micro organism

       O2 free radicals released from activated neutrophills & macrophages

       Endothelial damage

       ↑vascular permeability

       Tissue matrix damage

Plasma derived mediators

       Interlinked system


      Clotting system

      Kinin system

      Fibrinolytic system

      Complement system

       Hageman factor (Factor XII) – connects the other 4 system

Clotting system

       Results in formation of fibrinogen

       Thrombin converts fibrinogen to fibrin & fibrinopeptide

      ↑ vascular permeability

      Chemotaxis of leucocytes

      Anticoagulant activity

Fibrinolytic system

       Activated by plasminogen

       Plasminogen activator – plasminogen – plasmin-  breakdown of fibrin -  fibrinopeptides or fibrin split products


      Activation of factor XII

      Splits complement fraction C3to C3a– permeability factor

      Degrade fibrin to form fibrin split products

Complement system

Involves 2 pathways

       Classic pathway through antigen-antibody complexes

       Alternate pathway via non-immunologic agents such as bacterial toxins, cobra venoms and IgA

Anaphylatoxins (C3a, C5a, C4a)

      Activate mast cells and basophils to release of histamine

      cause increased vascular permeability

      augments phagocytosis

       C3b - an opsonin

       C5a -  chemotactic for leucocytes

       Membrane attack complex (MAC) (C5b-C9) is a lipid dissolving agent and causes holes in the phospholipid membrane

Chemical mediators of inflammation


       Chemical mediators are endogenous compounds released during inflammation which increases vascular permeability, bring about edema and destruction of inflammatory agents

       Chemical mediators of inflammation are derived from cell and plasma

       Cell derived mediators include histamine, serotonin, leukotrienes, platelet activating factors, cytokinines, prostaglandins

       Plasma derived mediators include kinin system, cltting and fibrinolytic system and clotting system

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