Synovial fluid macrophages and blood monocytes differ in their response to IL-4

IL-4 has been described as a potential anti-inflammatory molecule because of its ability in vitro to down-regulate human monocyte production of proinflammatory mediators. In this study, the activity of IL-4 on mononuclear cells and CD14+ macrophages from a site of chronic inflammation, namely, the joints of patients with rheumatoid and psoriatic arthritis, was investigated and compared directly with its activity on PBMC and monocytes from the same patients. In contrast to the response by blood monocytes, the response to IL-4 by synovial fluid cells was selective; IL-4 did not significantly suppress LPS-induced TNF-alpha production, but decreased CD14 expression to a similar extent in the two cell populations. IL-4 induction of monocyte/macrophage CD23 expression was investigated as a stimulatory response to IL-4, and although significantly increased on synovial fluid CD14+ cells by IL-4, the induction was considerably reduced compared with that measured for blood cells. Activation and differentiation in vitro of blood monocytes reduced their response to IL-4 for decreased TNF-alpha production and induction of CD23 and suggested that these biologic phenomena may contribute to the decreased responsiveness to IL-4 by synovial fluid monocytes/macrophages. Thus, IL-4 does not have the same anti-inflammatory properties in vitro on synovial fluid cells as on blood monocytes.