[Anti-inflammatory properties of interleukin-4].
Interleukin 4 (IL4) is a cytokine produced by T cells and mast cells/basophils. IL4 has a key role in IgE production and in the pathogenesis of atopic diseases. Disorders such as rheumatoid arthritis are characterized by increased production of proinflammatory cytokines and reduced production of IL4. Furthermore, rheumatoid T cells are of the TH 1 type, not producing IL4. In contrast, circulating IL4 has been detected in scleroderma patients, whose T cells are of the TH 2 type, producing IL4. Since IL4 inhibits the production of proinflammatory cytokines such as IL1, IL6, TNF alpha and IL8, we hypothesized that a deficit in IL4 production might be related to the pathogenesis of rheumatoid arthritis. Addition of IL4 strongly reduced the production of proinflammatory cytokines and expression of corresponding mRNA by synovial membrane pieces from RA patients. RA synovitis is also associated with marked proliferation of synoviocytes. Studies of synoviocytes showed that IL4 inhibited the growth promoting effect of PDGF and IL1 beta. IL4 also inhibited production of IL6 by juxta-articular bone pieces. IL4 was found to reduce disease activity and progression in various arthritis models. These anti-inflammatory and anti-proliferative properties suggest that IL4 may be of potential clinical value in RA. Conversely, as IL4 induces dermal fibroblasts to secrete collagen, IL4 might be involved in the pathogenesis of scleroderma.
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Département d'Immunologie et de Rhumatologie, Université Claude Bernard, Lyon, France.
D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D016207:Cytokines / Q000037:antagonists & inhibitors; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D015847:Interleukin-4 / Q000494:pharmacology* / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects; D009000:Monocytes / Q000187:drug effects
D016207:Cytokines; D015847:Interleukin-4
Propriétés anti-inflammatoires de l'interleukine 4.