Objective. Inflammation‐induced articular cartilage degradation is a major problem in rheumatoid arthritis (RA). Type 1 T cell activity (characterized by interferon‐γ/interleukin‐2 [IL‐2] production), and consequently, the production of the proinflammatory cytokines IL‐1 and tumor necrosis factor α (TNFα), have been reported to play a major role in cartilage damage. IL‐10 and IL‐4, both produced by type 2 T cells, are cytokines with the capacity to down‐regulate proinflammatory responses. The present study was undertaken to investigate the way in which these cytokines affect activated mononuclear cells (MNC) of RA patients in relation to human articular cartilage degradation in vitro.
Methods. MNC from synovial fluid and peripheral blood of RA patients were stimulated with bacterial antigen and treated with IL‐10 and/or IL‐4. Bacterial antigen is known to activate type 1 T cells and to induce proinflammatory IL‐1/TNFα–dependent cartilage damage. Cytokine production and effects of conditioned media, as well as effects of IL‐10 and IL‐4 on proteoglycan (PG) turnover (as a measure for cartilage damage), were determined.
Results. IL‐10 and IL‐4 inhibited proinflammatory cytokine production of stimulated RA MNC and completely reversed inhibition of cartilage PG synthesis induced by these stimulated RA MNC. IL‐10 was more potent than IL‐4 in this respect, and the combination of IL‐10 and IL‐4 had an additive effect. In addition, IL‐10 directly stimulated cartilage PG synthesis.
Conclusion. IL‐10 reverses the cartilage degradation induced by antigen‐stimulated MNC, and IL‐4 has an additive effect on this process. Furthermore, IL‐10 has a direct stimulatory effect on PG synthesis, and IL‐4, as a growth factor for type 2 T cells, can reduce the ratio of type 1 to type 2 T cell activity. These results provide evidence in favor of the use of a combination of the two cytokines in the treatment of RA.
Background-Despite improvement in short-term patient survival after heart transplantation (HTx), long-term survival rates have not improved much, mainly because of cardiac allograft vasculopathy (CAV). Cytokines and chemokines are considered to play an important role in CAV development. Interleukin-4 and interleukin-10 were expressed at the same level in both HTx groups and references. In HTxϩCAV, all CϩCR, but especially the T-helper 1 (TH1) CϩCR, were more abundant than in the HTxϪCAV and references. However, TH2 CCR4 expression did not differ significantly between both HTx groups. Conclusions-In coronary arteries with CAV, most T cells are CD4 ϩ and express human leukocyte antigen DR. These activated TH cells are mainly memory TH1 cells on the basis of their CϩCR profile and cytokine expression.
Methods and Results-We
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