[Contribution of cytokines to inflammatory mechanisms].
A large number of cytokines are found within foci of inflammation. Two of these cytokines, namely interleukin-1 (IL-1) and tumor necrosis factor (TNF), play a key role in orchestrating the mechanisms responsible for inflammation. These two cytokines induce production by many cells of lipid mediators, proteases, and free radicals, all of which play a direct role in development of the deleterious effects of inflammation. IL-1 and/or TNF exert cytotoxic effects on the vascular endothelium, cartilage, bone, muscle, or pancreatic beta-cell islets. Cytokines, including interferon gamma (IFN), IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF), amplify the inflammatory response by increasing production of IL-1 and TNF by macrophages. Macrophages also produce other cytokines, such as IL-8 and macrophage chemoattractant protein-1 (MCP-1), with chemoattractant properties that contribute to draw leucocytes to the site of inflammation. IL-6, produced in large amounts during inflammatory processes, induces the production of acute phase proteins by hepatocytes. IL-1, TNF, IL-11, leukemia inhibitory factor (LIF), and transforming growth factor beta (TGF beta) share this effect. TGF beta also has a number of anti-inflammatory effects. TGF beta, IL-4, and IL-10 inhibit production of IL-1 and TNF. Glucocorticoids also have this effect. Glucocorticoids can be produced as a result of a chain of events initiated by IL-1, TNF, and IL-6 and involving the neuro-endocrine axis. Other substances, such as IL-1 receptor antagonist (IL-1 ra) or soluble forms of the TNF receptors, can specifically inhibit the effects of IL-1 and TNF. Cascade production of cytokines, inhibition, negative feed-back, and synergistic mechanisms are parameters that illustrate the concept of "cytokine network" and aptly characterize the role of these mediators in the mechanisms of inflammation.
Cavaillon
J M
JM
Unité d'Immuno-Allergie, Institut Pasteur, Paris, France.
D000209:Acute-Phase Proteins / Q000096:biosynthesis; D001777:Blood Coagulation / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects; D016207:Cytokines / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D010450:Endopeptidases / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000187:drug effects; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D007375:Interleukin-1 / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*
D000209:Acute-Phase Proteins; D016207:Cytokines; D005609:Free Radicals; D007375:Interleukin-1; D011453:Prostaglandins; D014409:Tumor Necrosis Factor-alpha; D010450:Endopeptidases