Chemical mediators of inflammation

They drive the inflammatory process and are secreted by the cells or are derived from components of the plasma.

Derived chemical mediators of inflammation

Mediator	Source	Action
Histamine	Mast cells, basophils and platelets	Vasodilation, itching, pain, increased vascular permeability
5HT* or Serotonin	Chromaffin cells in GIT, mast cells, platelets, spleen, nervous system	Vasodilation, itching, pain, increased vascular permeability; In response to vessel injury, serotonin also causes vasoconstriction and platelet aggregation
Neuropeptides such as Substance P, neurokinin A, VIP, somatostatin	CNS and PNS	Increased vascular permeability, pain, mast cell degranulation
Bradykinin**	Mast cells and basophils	Vasodilation, increased vascular permeability, bronchoconstriction, pain, smooth muscle contraction

Mediators derived from arachidonic acid (eicosanoids)

Eicosanoids produced by the cyclo-oxygenase pathway

PGD2, PGE2	All cells, inflamed tissue, leukocytes, platelets	Increased vascular permeability, vasodilation, bronchodilation
PGF2 alpha	All cells, inflamed tissue, leukocytes, platelets	Vasodilation, bronchoconstriction
PGI2/prostacyclin	Mainly endothelial cells	Vasodilation, bronchodilation, inhibits platelet aggregation
Thromboxane A2	Platelets	Platelet aggregation, vasoconstriction, bronchoconstriction
Resolvins	Neutrophils, platelets, endothelial cells	Inhibit production of inflammatory cytokines; anti-inflammatory; inhibit formation of superoxide anion; inhibit transmigration and diapedesis.

Eicosanoids produced by the lipo-oxygenase pathway

Leukotrienes	Blood cells	LTB4 is chemotactic factor; LTC4, D4 and E4 together comprise SRS -A or slow reacting substances of anaphylaxis, they cause vasoconstriction, bronchoconstriction, increased vascular permeability and smooth muscle contraction.
5-HETE(5 hydroxyeicosatetraenoic acid)	Blood and tissue cells	Chemotactic for neutrophils
Lipoxins	Blood cells, endothelium	Anti-inflammatory; counterbalance actions of leukotrienes

Cytokines:polypeptides produced by activated leukocytes

IL 1	Macrophages	Increased leukocyte adherence, cytokine production, thrombogenicity, acute phase reactions#, proliferation of fibroblasts, fever, shock
TNF alpha	Macrophages	Shock, Increased leukocyte adherence, cytokine production, thrombogenicity, acute phase reactions, proliferation of fibroblasts
TNF beta	T cells	Increased leukocyte adherence, cytokine production, thrombogenicity, acute phase reactions, proliferation of fibroblasts
Gamma Interferon	T cells	Activation of macrophages and neutrophils

Other chemical mediators

PAF or platelet activating factor	Basophils, mast cells, leukocytes, platelets, endothelium	Increased vascular permeability, vasodilation at low doses; vasoconstriction at higher doses, bronchoconstriction, chemotaxis, leukocyte adhesion, platelet aggregation
Free radicals	Phagocytes	Endothelial cell damage, increased vascular permeability, activation of proteases
Nitric oxide	Macrophages	Vasodilation, microbicidal, anti-platelet

*5HT stands for 5 hydroxytryptamine, also known as serotonin.

** Bradykinin is derived from HMWK or high molecular weight kininogen by the action of the enzyme kallikrein and plasmin. Bradykinin is degraded by enzyme ACE and peptidases.

#fever, leukocytosis

Plasma derived chemical mediators of inflammation: They include the clotting system, kinin system, fibrinolytic system and complement system. Factor XII or Hageman factor is activated by bacterial endotoxins and by contact with the basement membrane. Activated factor XII, in turn, activates the clotting, kinin and fibrinolytic systems, which in turn activate the complement system.

i) Kinin system: Activated factor XII catalyzes the conversion of pre-kallikrein to kallikrein, which then converts HMWK to bradykinin.

ii) Clotting system: Activated factor XII initiates the clotting cascade ending with the formation of fibrinogen. Plasmin converts fibrinogen to fibrinopeptides, which increase vascular permeability, act as chemotactic factors for neutrophils and have anticoagulant activity.

iii) Fibrinolytic system: Plasminogen activator converts inactive plasminogen from the plasma, to active plasmin. Plasminogen activator is derived from endothelial cells, kallikrein and leukocytes. Plasmin lyses fibrin, forming fibrinopeptides and fibrin split products, which increase vascular permeability. Plasmin also activates factor XII and cleaves C3 to C3a.

iv) Complement system: Complement system is activated by the classic or alternate pathway to yield potent mediators of inflammation.

Complement	Action
C3b	Opsonization
C5a	Chemotaxis
C3a, C4a, C5a	Anaphylotoxins, activate mast cells and basophils to release histamine
C5b-C9	Membrane attack complex (MAC), forms holes in cell membrane