Mediators of Inflammation

Mediators of Inflammation Mediators of Inflammation Cell derived Plasma derived Preformed Synthesised de novo 8. Complements 1. Histamine 4. NO 9. Kinins 2. Serotonin 5. Platelet Activating 10. Coagulation factors Factor (PAF) 3. 10/2° Granules of Neutrophil 6. Arachidonic acid Metabolite 7. Interleukins / Cytokines HISTAMINE 04:08 Source : i) Mast cells ii) Basophils iii) Patelets Function i) Vasodilation ii) Increased vascular permeability iii) Endothelial activation

SEROTONIN 05:28 a.k.a SHT (5-Hydroxy Tryptamine) Source i) Platelets ii) Enterochromaffin cells (GIT) Function i) vasoconstriction PRIMARY AND SECONDARY GRANULES 06:40 1° Azurophillic 2° Specific granules NITRIC OXIDE 07:10 Nitric oxide (NO) Nitric oxide Synthase - NOS Arginase Arginine citruline NOS NO Function i) Vasodilation ii) Smooth muscle Relaxation iii) ROS (Reactive oxygen Species)

PLATELET ACTIVATING FACTOR 09:50 It is phospholipid derived mediator Source : Plasma membrane of cells Eg: i) Platelets ii) Neutrophils iii) Mast cell iv) Endothelium Function : i) Platelet aggregation ii) permeability iii) Bronchoconstriction iv) Vasodilation (in lower concentration), vasoconstriction (in higher concentration). ARACHIDONIC ACID METABOLITE 13:09 20C Polyunsaturated FA Activated by Mechanical, chemical, Physical stimuli. C DEPARTMENT Phospholipase A2 Phospholipid Arachidonic Acid

Arachidonic Acid cyclooxygenase 5-lipooxygenase cox-2 Cox-1 PGG2 5-HPETE SHETE PG H2 LT A4 LTB4 PG I 2 TxA2 PGD2.E2 TB4 LT C4 12-LOX LT D4 Lipoxins : LXAG , LXB4 PG I2 TxA2 PGD2.E2 Prostacyclin Thromboxane A2 Prostaglandin vasodilation vasoconstriction vasodilation platelet platelet vascular aggregation aggregation permeability fever (PGE2) LT B4- Chemokine LT C4 Bronchoconstriction LT D4 vascular permeability. Lipoxins: LT Au. LTB4 Anti-inflammatory chemotaxis Neutrophil adhesion

Phospholipase A2 - - by Steroids COX 1,2 - - by COX Inhibitors (Aspirin, Indomethacin) 5 lipooxygenase - - by Lox Inhibitors Leukotriene - - by Leukotriene Receptor Antagonists. INTERLEURINES AND CYTOKINES 28:00 proteins released by activated cells (lymphocytes, Macrophage, Neutrophils, Endothelial cells, Epithelial cells, APC) which take part in inflammation and immune reaction Eg: i) Acute Inflammation: TNF IL-17 IL-1 Chemokines IL-6 ii) Chronic Inflammation IL-12 IFN-r IL-17 Most important in Acute Inflammation: TNF x IL-1

IL-1 and TNF-X Source: i) Mast cell ii) Macrophages iii) Tcells Function : -They stimulate/Activate endothelium to express adhesion molecules, T permeability of vessels - stimulate Neutrophils to release IL-1, IL-6, Chemokines. - stimulate Macrophage to release IL-1, IL-6, Chemokines. - Systemic Effects : Fever - Acute Phase Reactants synthesis Acute Phase Reactants Proteins synthesized by liver in response to cytokines. Eg: IL-1, IL-6, TNF-x etc. IL-1, 11-6, TNF - x stimulate Liver Synthesixe proteins.

Proteins synthesized by Liver: Eg: Fibrinogen: TESR C-Reactive Protein (CRP) (c-Capsular Polysaccharide of Pneumococcus) Ferritin concentration, + ve APR Ceruloplasmin Hepcidin Haptoglobulin Serum Amyloid. Transferrin Albumin concentration, - ve APR Transthyretin COMPLEMENTS 43:00 Collection of Plasma proteins which has role in host defence. Eg: i) Opsonization : opsonins C3b,C4b,C56 ii) Cellysis: C5-C9 (Membrane Attack Complex) iii) Inflammation : Csa chemotaxis

iv) Inflammation: Csa (Chemotaxis) v) Anophylotoxins: C3a, C5a KININS 46:03 vasoactive peptides Eg : i) Kininogens In serum : High Molecular weight Kininogen (HMWK) Kallikerin Bradykinin: vasodilation vascular permeability Smooth muscle constriction Pain (if injected into skin) Factor XII HMWK Activates Factor XIIa coagulation Pathway. Inflammation is Pro coagulant state