INFLAMMATION Part 6 Chemical Mediators CYTOKINES Interleukins amp Chemokines

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Click here to view Inflammation part 5: • INFLAMMATION Part 5: Chemical Mediato... • • 5. Cytokines are low molecular weight regulatory proteins or glycoproteins Secreted by white blood cells and various other cells in the body in response to a number of stimuli. Mainly by activated lymphocytes, macrophages, and dendritic cells, but also endothelial, epithelial, and connective tissue cells Mediate INFLAMMATORY and IMMUNE reactions • 6. Cytokine is actually a general term Other names Interleukins lymphokines Monokines Chemokines Produced by one leukocyte ad act on other leukocyte Produced by Lymphocytes Produced by Monocytes Cytokines which are having chemotactic activities Interferons Involved in antiviral responses Colony stimulating factors Supports the growth of blood cells • 7. Actions: general Properties ENDOCRINE ACTION Circulation Distant cell • 8. PARACRINE ACTION Nearby cell • 9. AUTOCRINE ACTION • 10. Other Properties Exhibited by cytokines Pleiotrophic Redundancy Cascade Induction Synergy Antagonism Different cell types can secrete the same cytokine or a single cytokine can act on several different cell types Similar functions can be stimulated • 11. • Mediate the leukocyte cross-talk (hence the name) • Up to 38 ILs have been so far identified, numbered according to the order of discovery • Involved in the pathogenesis of human inflammatory/autoimmune diseases INTERLEUKINS • 12. • The interleukins and other cytokines which have a significant role in Acute inflammation are • IL-1 • IL-6 • IL-17 • TNF-alpha • Chemokines • 13. • Two most important cells which are the sources of most of the cytokines are • MACROPHAGES T LYMPHOCYTES INTERLEUKIN-1 INTERLEUKIN-6 TNF-α INTERLEUKIN-17 TNF-β • 14. INTERLEUKIN-1 INTERLEUKIN-6 INTERLEUKIN-17 Macrophages , Fibroblasts, endothelial cells few epithelial cells Macrophages, Fibroblasts endothelial cells few epithelial cells T Lymphocytes Stimulates expression of endothelial adhesion molecules Emigration of neutrophils macrophages Secretion of other cytokines Fever Systemic Response: Production of Acute Phase Reactants from liver Particularly important in inducing B-Cells to differentiate into antibody producing Cells (Plasma Cells) Recruitment of neutrophils and monocytes Secretion of other cytokines like IL-6, G-CSF, GM-CSF, IL-1β, TNF-α, chemokines • 15. TUMOR NECROSIS FACTOR -α Macrophages cells, Fibroblasts endothelial cells few epithelial cells Stimulates expression of endothelial adhesion molecules Emigration of neutrophils macrophages Secretion of other cytokines Fever Regulates energy balance by promoting lipid and protein catabolism and by suppressing appetite TUMOR NECROSIS FACTOR –β B T lymphocytes only Cellular cytotoxicity Development of spleen and lymph nodes Not much role in acute inflammation • 16. CHEMOKINES Macrophages cells endothelial cells Family of Small 8-10kD proteins Act as chemoattractant for leukocytes They Bind to 7 transmembrane G protein coupled receptors They direct the movement of circulating leucocytes to the site of inflammation and injury. • 17. C chemokines CC chemokines CXC chemokines CX3C chemokines Adapted from ©Kohidai L TYPES • 18. CC chemokines . CC chemokines induce the migration of monocytes Also NK cells and dendritic cells. Examples: Monocyte chemoattractant protein-1 (MCP-1 or CCL2) Induces monocytes to leave bloodstream and enters the tissue to become macrophages CCL5 ( RANTES) Regulated on Activation, Normal T Cell Expressed and Secreted Attracts cells such as T cells, eosinophils and basophils • 19. The two N-terminal cysteines are separated by an amino acid, represented in this name with an X . CXC chemokines induce the migration of Neutrophils LymphocytesExamples: Interleukin-8 (IL-8) Induce the migration of Neutrophils CXCL13 Induce the migration of Lymphocytes CXC chemokines • 20. C chemokines Has only two cysteines Examples: XCL1 lymphotactin-α and XCL2 lymphotactin-β. Induces migration of lymphocytes • 21. CX3C chemokines Examples: Fractalkine (or CX3CL1) Both a chemoattractant Chemotactic for monocytes, natural killer (NK) cells, and T cells and as an adhesion molecule • 23. ROLE OF OTHER CYTOKINES IL12, IL17 IFN-γ are involved in chronic inflammation Interferons Also Involved in antiviral responses Colony stimulating factors Supports the growth of blood cells eg.IL7,GM-CSF etc. • 24. APPLIED ASPECTS IL-6 receptor antagonists are used in the treatment of rheumatoid arthritis IL-17 antagonists are very effective in psoriasis and other inﬂammatory diseases. Inhibiting cytokines can prevent some harmful effects of inflammation and immune reaction Inflammation is a double edged sword! Interferons used in the treatment of viral diseases GM-CSF increases white cell count, used after bone marrow transplantation, Chemotherapy induced neutropenias

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