INHIBITION OF THE PRODUCTION OF PROINFLAMMATORY CYTOKINES AND IMMUNOGLOBULINS BY INTERLEUKIN-4 IN AN EXVIVO MODEL OF RHEUMATOID SYNOVITIS

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-1-beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), 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-1-beta or TNF-alpha, and explants produced more IgG than IgM. In contrast, IL-4 and interferon-gamma 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.