Chemical mediators
- 1. Mediators of inflammation Dr Sehrish Ahmed
- 2. Overview • General Properties • Types of mediators • Clinical aspects
- 3. What are they??? Mediators of inflammation are the substances that INITIATE & REGULATE the inflammatory reactions
- 5. Properties • Specific stimulus • Short lived • Cascade reaction
- 8. Histamine heat, cold, irradiation, trauma C3a & C5a: Anaphylatoxins IL-1 & IL8.
- 10. Serotonin 5- Hydroxytryptamine Action similar to histamine
- 12. Arachidonic Acid Ca Activation of Phospholipase A2Free AA
- 14. LEUKOTRIENES Leukocytes and mast cells More potent than Histamine PROSTAGLANDINS Mast cells, macrophages, endothelial cells LIPOXINS
- 15. Systemic Manifestations of Inflammation prostaglandins are involved in the pathogenesis of pain and fever PGE2 makes the skin hypersensitive to painful stimuli, and causes fever during infections
- 16. What did we understand so far?? The metabolites of arachidonic acid i.e PG, LT and Lipoxins mediates – Vasodilation – Vasoconstriction – Bronchodilation – Bronchoconstriction – Platelet aggregation and inhibition – Chemoattraction – Inhibition of chemotaxis CAN MEDIATE POSSIBLY EVERY STEP OF INFLAMMATION
- 18. CYTOKINES
- 19. OTHER NAMES • INTERLEUKINS • LYMPHOKINES • INTERFERONS • CHEMOKINES • MONOKINES
- 20. INTERLEUKINS • Mediate the leukocyte cross- talk • Upto 38 ILs have been identified
- 21. Significant role in Acute inflammation: • IL 1 • IL 6 • IL 17 • TNF Alpha • Chemokines
- 22. Sources of most of cytokines are MACROPHAGES T LYMPHOCYTES IL-1 IL-6 TNF-Alpha IL-17 TNF-Beta
- 23. LOCAL INFLAMMATION SYSTEMIC PROTECTIVE EFFECT SYSTEMIC PATHOLIGICAL EFFECT
- 24. TNF antagonists have been remarkably effective in the treatment of chronic inflammatory diseases, • rheumatoid arthritis, • psoriasis, • inflammatory bowel disease
- 25. CHEMOKINES (Macrophages & Endothelial cells) a family of small (8–10 kD) proteins that act primarily as chemo-attractants for specific types of leukocytes • 4 types
- 26. C Chemokine Lymphocytes CC Chemokines Monocyte, Eosinophils CXC Chemokine Neutrophils CX3C Chemokine Monocytes and T cells (Both chemoattractant and adhesion molecule)
- 28. Role of other cytokines
- 29. PLASMA DERIEVED
- 34. Kinins
- 35. • Histamine, ProstaglandinsVasodilation • Histamine, C3a and C5a, Leukotrienes C4, D4, E4 Increased vascular permeability • TNF, IL-1, Chemokines, C3a, C5a, Leukotriene B4 Chemotaxis, leukocyte recruitment and activation. • IL-1, TNF, ProstaglandinsFever • Prostaglandins, BradykininPain
- 36. Thankyou!
Editor's Notes
- #31: The complement system is a collection of soluble proteins and their membrane receptors that function mainly in host defense against microbes and in pathologic inflammatory reactions.
- #35: Kinins are vasoactive peptides derived from plasma proteins, called kininogens, by the action of specific proteases called kallikreins. The enzyme kallikrein cleaves a plasma glycoprotein precursor, high-molecular-weight kininogen, to produce bradykinin. Bradykinin increases vascular permeability and causes contraction of smooth muscle, dilation of blood vessels, and pain when injected into the skin.