The presence of interleukin‐13 in rheumatoid synovium and its antiinflammatory effects on synovial fluid macrophages from patients with rheumatoid arthritis

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Abstract
Objective. To study the production of interleukin-13 (IL-13) in rheumatoid synovium and the effects of recombinant IL-13 on the phenotype and function of synovial fluid (SF) macrophages and T cells derived from patients with rheumatoid arthritis (RA). Methods. The presence of IL-13 in SF was studied using an IL-13—specific enzyme-linked immunosorbent assay (ELISA); the production of IL-13 was studied in SF mononuclear cells (SFMC) by reverse transcriptase—polymerase chain reaction. The effects of recombinant IL-13 on cytokine production by and phenotype of SFMC were evaluated using cytokine-specific ELISAs and flow cytometry, respectively. The effect of IL-13 on the proliferation of SFMC was determined by 3H-thymidine incorporation. The production and the effects of IL-13 were compared with those of IL-4. Results. IL-13 was present in 27 of 28 SF samples, and IL-13 messenger RNA (mRNA) was detectable in SFMC. Importantly, IL-13 levels were significantly higher than those of IL-4, and IL-13 protein and mRNA were expressed in several samples, although IL-4 synthesis was undetectable. Recombinant IL-13 significantly reduced the production of IL-1β and tumor necrosis factor α and the expression of CD16 and CD64 by SF macrophages, whereas the expression of HLA—DR and CD23 was increased. These effects on SF macrophages were similar to those observed with IL-4, but in contrast to IL-4, IL-13 had no growth-promoting effect on SF T cells. Conclusion. IL-13 is consistently present in rheumatoid synovium. The ability of exogenous IL-13 to decrease the production of proinflammatory cytokines by SFMC suggests that it may have therapeutic potential in the treatment of patients with RA.