Stimulation of Interleukin 6‐Like B‐Cell Differentiation Factor Production in Human Adherent Synovial Cells by Recombinant Interleukin 1

Abstract

Abnormal production of immunoglobulin 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-cell differentiation by their spontaneous production of B-cell differentiation factor (BCDF). The regulation of the production of this factor, however, has not yet been described. We investigated the effects of recombinant interleukin 1 alpha and beta (rIL-1 alpha and rIL-1 beta) on the production of BCDF in ASC. Increased production of BCDF was observed with increased rIL-1 concentration. Production of BCDF was detected 3 h after exposure of ASC to rIL-1 and increased throughout a 48-h culture. This BCDF, assayed on SKW6-CL4 cells, was found to share a common active site with interleukin 6. The effect of rIL-1 was almost neutralized by anti-IL-1 antibody and the addition of polymyxin B did not diminish the effect of rIL-1, indicating that rIL-1 itself stimulates ASC in vitro. These results suggest that IL-1 may play a regulatory role in the production of BCDF in synovial tissue.

Interleukin‐1β induces synthesis and secretion of interleukin‐6 in human chondrocytes

“…Recent studies from several laboratories have demonstrated that the steady state metabolism of chondrocytes is affected by factors such as insulin-like growth factors IGF-I and IGF-II [5,6], transforming growth factor [7,8], and interleukin-1 (IL-1) [9][10][11][12][13][14][15]. Increased concentrations of interleukin-6 have been found in the synovial fluid of patients with osteoarthritis, rheumatoid arthritis, and crystal-related joint diseases [16][17][18]. Since IL-1 appears to be the major stimulator of interleukin-6 (IL-6) synthesis in many different cell types (reviewed in [19]), we asked the question, whether chondrocytes can also be stimulated to synthesize IL-6.…”