Interleukin-6 and soluble interleukin-6 receptors in the synovial fluids from rheumatoid arthritis patients are responsible for osteoclast-like cell formation

Oxford University Press (OUP) - Tập 11 Số 1 - Trang 88-95 - 1996
Shigeru Kotake1, Kazuto Sato1, Kang Jung Kim1, Naoyuki Takahashi2, Nobuyuki Udagawa2, Ichiro Nakamura2, Akira Yamaguchi3, Tadamitsu Kishimoto4, Tatsuo Suda2, Sadao Kashiwazaki1
1Institute of Rheumatology, Tokyo Women's Medical College, Wakamatsucho, Tokyo, Japan
2Department of Biochemistry, School of Dentistry, Showa University, Tokyo, Japan
3Department of Oral Pathology, School of Dentistry, Showa University, Tokyo, Japan
4Department of Medicine III, Osaka University Medical School, Osaka, Japan

Tóm tắt

Abstract Chronic immune responses and inflammatory reactions in rheumatoid arthritis (RA) often cause severe destruction of cartilage and bone, but its mechanism is still a matter of controversy. We reported that interleukin-6 (IL-6) alone does not induce osteoclast formation, but soluble interleukin-6 receptors (sIL-6R) triggered the formation in the presence 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 RA. Although the frequency of patients having osteoclast-like multinucleated cells in synovium derived from the knee joint was not significantly different between RA (65%) and osteoarthritis (OA) patients (43%), the number of osteoclast-like cells found in the synovium was greater in the former than in the latter. Multinucleated cells obtained from RA synovium expressed the osteoclast-specific phenotype such as tartrate-resistant acid phosphatase, carbonic 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 that the RA synovial fluids contained sufficient IL-6 and sIL-6R to induce osteoclastogenesis. When synovial fluids from RA and OA patients were added to the cocultures, some of the RA synovial fluids containing high levels of IL-6 and sIL-6R stimulated osteoclast-like cell formation, which was strikingly inhibited by adding anti-IL-6R antibody simultaneously. 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.

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Tài liệu tham khảo

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Oxford University Press (OUP)

Tập 11 Số 1

88-95

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