Scand. J. Immunol. 29, 289-297. 1989 Stimulation of Interleukin 6-Like B-Cell Differentiation Factor Production in Human Adherent Synovial Cells by Recombinant Interleukin 1 M. HARIGAI. M. HARA. K. NORIOKA. A. KITANl. T. HIROSE. K. SUZUKI. M. KAWAKAMI. K. MASUDA. M. SHINMEI. M. KAWAGOE & H. NAKAMURA First Departmcni of Medicine and Departmcni of Orlhopaedics. National Defence Medical College, Tokorozawa. Japan Harigai. M.. Hara. M.. Norioka. K.. Kitani, A.. Hirose. T.. Suzuki. K.. Kawakami. M., Masuda. K.. Shinmei, M., Kawagoe, M. & Nakamura. !I. Stimulation of Interleukin 6-Like B-Cell DilTerentialion Factor Production in Human Adhcreni Synovial Cells by Recombinant Interleukin \. Scand. J. Immunol. 29, 289 297, 1989 Abnormal production of immunogiobulin in the joint space is frequently observed in patients with rheumatoid arthritis (RA). We have previously demonstrated that adherent synovial cells (ASC) from patients with RA are involved in B-cel! dilTerentialion by tlieir spontaneous produclion of B-cell diRcrcntialion factor (BCDF). The regulation of the production of this factor, however. ha.s noi yet been described. We investigated the effects of recombinant interteukin l^i and /( (rlL-Ix and rIL-l/i) on the production of BCDF in ASC. Increased produclionof BCDF was observed with increased rl L-I concentration. Production ofBCDi-was detected 3 hafterexposureof ASCtorlL-l and increased throughout a 48-h culture. This BCDF. assayed on SKW6-CL4 cells, was found to share a eommon active site with interleukin 6. The effect of rIL-I was almost neutralized by anti-IL-1 antibody and the addition of polymyxin Bdid not diminish the effect of rIL-1. indicating that rlL-l itself stimulates ASC in vitro. These results suggest that IL-1 may play a regulatory role in the production of BCDF in synovia! tissue. Ma.sako Hara. First Department of Medicine. National Defence Medical College. 3-2 Namiki, Tokorozawa. Saitama. 359. Japan Rheumatoid arthritis (RA) is a systemic disease characterized by a chronic inflammation of the synovium and by the presence ofviirious immuno- logical abnormahlies. Prominent among these is the enhanced produclion of immunoglobulins by B cells that have infiltrated ihe synovium. Recently, we demonstrated the spontaneous pro- duclion of interleukin 6-like B-cell differentiation factor (IL-6-likc BCDF) in adherent synovial cells (ASC) [12]. Since B ceils are known to differentiate into antibody-secreting cells in the presence of BCDF 118]. our results suggested the possibility of synovial cells being able to induce B- cell differentiation in vivo. The regulation of the lL-6-like BCDF production in ASC. however. has not been studied so far. Interleukin I (IL-1) has been known to elicit a variety of responses from connective tissue cells. In fact. IL-l has been found in the synovial fluid of palients with inflammatory joint diseases [35] and is thought to be involved in the pathogenesis of diseases such as RA. IL-l regulates ASC to produce several infiammatory mediators such as serine proteases [25]. prostaglandin E;, and tissue plasminogen activator [21. 26]. IL-1 also stimu- lates fibrobtasts to proliferate [17] and to produce lL-6 [9]. We therefore investigated the effects of IL-l on IL-6-likc BCDF production in ASC. In this study, we demonstrate that recombinanl IL-la and P (rIL-la and /() can induce the production of IL-6-hke BCDF in ASC. The effectsof these two forms of I L-I are comparable. Thus. IL-l may play a regulatory role in the production of IL-6-like BCDF in ASC. 289