Chemical Mediators of Inflammation:
Chemical mediator of inflammation are a large and increasing no of endogenous substance which mediated the process of acute and chronic inflammation. Chemical mediators of inflammation must have some comman properties as under:
- Either they should release from the cells or derived from the plasma proteins. Cell-derived mediators are released either from their storage in cell granules or synthesised inthe cells. Most common site of synthesis of plasma-derived mediated is the liver.
- All mediator are released in response to certain stimuli. They may be endogenous or exogenous stimuli.
- Mediator act on different targets to produce same or different action.
- Chemical mediators of inflammation are having a short span of life after release they rapidly removed from body.
- In general, the spectrum of action of different chemical mediators of inflammations is increased vascular permeability, vasodilation, chemotaxis, fever, pain and tissue damage.
|Vasoactive amines||Histamine, 5-HT, Neuropeptides.|
|Arachidonic acid derivatives||a) by – Cyclooxygenase pathway – Prostaglandin, Thromboxane, Prostacycline.|
b) by – Lipooxygenase pathway – 5-HPETE, Leucotienes, Lipoxins.
|Cytokines||Interleukins ( IL-1, IL-6, IL-8, IL-12); TNF – ∝ , TNF-ß, IFN-γ|
|Platelets activating Factors|
Histamine: It is stored in mast cell , basophils, and platelets. Release in response to various stumulis. The main actions are vasodilation, Permeability, iching and pain. Stimulation of the mast cell and basophils also release product of arachidoic acid metabolism.
5- HT: Present in platelet and endocroma cells of GIT. The action is silmilar to that of Histamine but less potent.
Neuropeptides: Substance P, Neurokinein A, vasoactive intestinal polypeptide (VIP), Somatosatin are shows effects incresed permeability, induce pain, mast cell degranulation.
Cytokines: Cytokines are the polypeptides substances produces by activated lymphocytes and activated monocytes. They are Interleukins (IL-1, IL-6, IL-8, IL-12, IL-17), TNF family ( TNF-α, TNF-β) and Interferon family (IFN-γ).
Platelets Activating Factors: It is released from basophils or mast cell by the influence of IgE apart from aggregation factor of platelets. They increase permeability, vasodilation, chemotaxis and bronchoconstriction.
Free Radicals: They are Oxygen derived released from neutrophils and macrophages includes O2, OH radicals. They damage endothelial cell to increase permeability and activate protease. Nitric acid derivatives cause vasodilatiopn and anti-platelet activating agents.
Arachidonic acid metabolites:
Plasma Protein – derived Mediators:
|The Kinin system||Kallikrein, Bradykinin|
|The Clotting system||Fibrin, Fibrinopeptides|
|The Fibrinolytic System||Plasmin|
|The Complement system||C3a, C3b, C5a, MAC|
Plasma-derived mediators include various products derived from activation and interaction of four interlinking system- kinin, clotting, fibrinolytic and complement. Each of these system has its inhibitors and accelerattion in plasma with negative and positive feedback mechanism respectively.
Hageman factor of clotting system play a key role in interaction of the four systems.
The Kinin System:
This system on activation by factor XIIa generate bradykinin as shown. Bradykinin act in the early stage of inflammation and its effects include
- Smooth muscle contraction
- Increased vascular permeability
The Clotting System:
Factor XIIa initiates the cascade of the clotting system resulting in formation of fibrinogen which acted upon by thrombin to form fibrin and fibrinopeptides. The action offibrinopeptides in inflammation are
- Increased vascular permeability
- Chemotaxis for leucocytes
- Anti-coagulant activity
The Fibrinolytic System:
Plasminogen activator acts on plasminogen present as component of plasma protein to form plasmin. Futher breakdown of fibrin by plasmin forms fibrinopeptide. The action of plasmin are
- Conversion of fibrin to fibrinopeptides and by following complementory system it forms C3a.
The Complementary System:
Complementory system is a group of 30 distrubuted proteins that include normal serum protein, cell receptor, and cell surface protein. The system is important part of innate and adaptive immune system.
Classical Pathway: It is trigred by antigen-IgG or IgM from Ag-Ab complex, which inturn breakdown C3 to produce active cleavage produces C3a and C3b.
Alternate Pathway: Ith can triggered by bacterial toxin when come in contact with cell surface proteins or other and by breakdown C3 to produce C3b, C6, C7, C8,.
Mannose-binding Lectin Pathway(MBL): MBL binds to mannose resides on microbial surface and activate MBL-associated serine proteases. These inturn split C4 into C4a, C4b together for C3 convert as in Classic pathway.
Chemical Mediators of Inflammation is released in response to any external stimuli or injury and play avital role in the wound healing process and reaparing of tissues. For more pharma info click here.