Inhibition of the production of proinflammatory cytokines and immunoglobulins by interleukin‐4 in an ex vivo model of rheumatoid synovitis

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Abstract
Objective. To assess the spontaneous production of proinflammatory cytokines and immunoglobulins in rheumatoid arthritis (RA) synovitis and modulation by interleukin‐4 (IL‐4).Methods. We developed an ex vivo model of RA synovitis using pieces of RA synovium, and have studied the regulation of the production of IL‐1β, IL‐6, tumor necrosis factor α (TNFα), IgM, and IgG.Results. Spontaneous production of proinflammatory cytokines in vitro was active, with prolonged cytokine gene transcription and translation. IL‐6 was produced at higher levels than either IL‐1β or TNFα, and explants produced more IgG than IgM. In contrast, IL‐4 and interferon‐γ were undetectable. When pieces of synovium were incubated in the presence of IL‐4, reduction of spontaneous proinflammatory cytokine and Ig production was observed.Conclusion. These results extend the observations of the antiinflammatory properties of IL‐4 to an ex vivo situation, and provide the rationale for the clinical use of IL‐4 in RA.