Novel pro-inflammatory interleukins: potential therapeutic targets in rheumatoid arthritis.
Among potential targets for nonspecific anti-inflammatory immunointervention, three pro-inflammatory interleukins (ILs) have recently been found to play a pivotal role in rheumatoid arthritis (RA). IL-15 has both chemoattractant and proinflammatory properties and may promote bone destruction. IL-17, a product of T lymphocytes, has proinflammatory effects and induces production of metalloproteinases such as MMP-1. IL-18 not only has proinflammatory, angiogenic, and chemoattractant effects but also promotes cartilage destruction. These cytokines are potential targets for specific or nonspecific anti-inflammatory therapy. Thus, blocking IL-15 by its receptor reduces the severity of experimental collagen-induced arthritis (CIA). In this model, IL-17 levels fall after administration of anti-inflammatory cytokines such as IL-4 or IL-13. Finally, monoclonal anti-IL-18 antibodies prevent streptococcal cell wall arthritis, and IL-18 binding protein, which is a naturally occurring IL-18 inhibitor, prevents CIA.
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UPRES EA-3408 et Formation de Recherche en Immunopathologie et Immuno-Intervention Articulaires (Association Claude Bernard), Rheumatology Department (CHU Avicenne, AP-HP), UFR Léonard de Vinci Bobigny, Université Paris 13, France.
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D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D002478:Cells, Cultured; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology; D018793:Interleukin-13 / Q000627:therapeutic use; D019409:Interleukin-15 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D020382:Interleukin-18 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology; D015847:Interleukin-4 / Q000627:therapeutic use; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout
D018836:Inflammation Mediators; D018793:Interleukin-13; D019409:Interleukin-15; D020381:Interleukin-17; D020382:Interleukin-18; D007378:Interleukins; D015847:Interleukin-4