INTERLEUKIN-6 AND SOLUBLE INTERLEUKIN-6 RECEPTORS IN THE SYNOVIAL-FLUIDS FROM RHEUMATOID-ARTHRITIS PATIENTS ARE RESPONSIBLE FOR OSTEOCLAST-LIKE CELL-FORMATION

Chronic immune responses and inflammatory reactions in rheumatoid arth ritis (RA) often cause severe destruction of cartilage and bone, but i ts mechanism is still a matter of controversy. We reported that interl eukin-6 (IL-6) alone does not induce osteoclast formation, but soluble interleukin-6 receptors (sIL-6R) triggered the formation in the prese nce of IL-6 in cocultures of murine osteoblastic cells and bone marrow cells. In this study, we examined the involvement of sIL-6R and IL-6 in joint destruction in patients with Rk Although the frequency of pat ients having osteoclast-like multinucleated cells in synovium derived from the knee joint was not significantly different between RA (65%) a nd osteoarthritis (OA) patients (43%), the number of osteoclast-like c ells found in the synovium was greater in the former than in the latte r. Multinucleated cells obtained from RA synovium expressed the osteoc last-specific phenotype such as tartrate-resistant acid phosphatase, c arbonic anhydrase II, vacuolar proton-ATPase and vitronectin receptors at similar levels to those from a human giant cell tumor of bone. The concentration of both IL-6 and sIL-6R was significantly higher in the synovial fluids from patients with RA than with OA. The concentration of IL-6 and sIL-6R correlated well with the roentgenologic grades of joint destruction Dose-response curves for human IL-6 and human sIL-6R in inducing osteoclast-like cell formation in cocultures indicated th at the RA synovial fluids contained sufficient IL-6 and SIL-6R to indu ce osteoclastogenesis., When synovial fluids from RA and OA patients w ere added to the cocultures, some of the RA synovial fluids containing : high levels of IL-6 and sIL-6R stimulated osteoclast-like cell forma tion, which was strikingly inhibited by adding anti-IL-6R antibody sim ultaneously, These results suggest that IL-6 in the RA synovial fluids is at least in part responsible for joint destruction in the presence of sIL-6R through osteoclastogenesis.