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

J Bone Miner Res. 1996 Jan;11(1):88-95. doi: 10.1002/jbmr.5650110113.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antigens, CD / metabolism*
  • Arthritis, Rheumatoid / etiology
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology*
  • Cells, Cultured
  • Female
  • Humans
  • Interleukin-6 / metabolism*
  • Male
  • Mice
  • Middle Aged
  • Osteoarthritis / immunology
  • Osteoarthritis / pathology
  • Osteoblasts / pathology
  • Osteoclasts / enzymology
  • Osteoclasts / immunology*
  • Osteoclasts / pathology*
  • Phenotype
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-6
  • Solubility
  • Synovial Fluid / immunology*
  • Synovial Membrane / enzymology
  • Synovial Membrane / immunology
  • Synovial Membrane / pathology

Substances

  • Antigens, CD
  • Interleukin-6
  • Receptors, Interleukin
  • Receptors, Interleukin-6
  • Acid Phosphatase