Treatment of rheumatoid synovitis with anti-reshaping human interleukin-6 receptor monoclonal antibody: use of rheumatoid arthritis tissue implants in the SCID mouse model

Arthritis Rheum. 1998 Nov;41(11):2014-21. doi: 10.1002/1529-0131(199811)41:11<2014::AID-ART17>3.0.CO;2-T.

Abstract

Objective: To examine the effect of anti-reshaping human interleukin-6 receptor monoclonal antibody (anti-rsHuIL-6R mAb) on patients with rheumatoid arthritis (RA), using SCID mice in which human RA synovial tissue has been grafted (SCID-HuRAg).

Methods: Tissue from human RA pannus was implanted subcutaneously in the backs of 69 SCID mice. Differences from human RA were examined pathologically. Anti-rsHuIL-6R mAb (100 microg) was administered intraperitoneally to mice once a week for 4 weeks. The implanted tissue was removed from the SCID-HuRAg mice on the fifth week after the initial treatment and examined pathologically. A group of SCID-HuRAg mice treated with control mAb, an auranofin-treated group, and an untreated group were used as controls. A total of 32 mice (8 in each group) were studied.

Results: Histologic characteristics of the implanted tissues in SCID-HuRAg mice were very similar to those of human RA even 2 months after implantation. In addition, the presence of CD4-, CD8-, CD20-, IL-6-, tumor necrosis factor alpha-, tartrate-resistant acid phosphatase (TRAP)-, matrix metalloproteinase 1 (MMP-1)-, and MMP-9-positive cells was confirmed by immunohistochemical staining. A significant decrease in the number of inflammatory cells, MMP-positive cells, and TRAP-positive cells was observed in the anti-rsHuIL-6R mAb treatment group as compared with the control groups.

Conclusion: The SCID-HuRAg mouse is a useful model for evaluating the effectiveness of antirheumatic drugs. Anti-rsHuIL-6R mAb may have an antiinflammatory effect on RA synovitis and an inhibitory effect on osteoclasts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Antibody Affinity
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / therapy*
  • Disease Models, Animal
  • Graft Survival / immunology
  • Humans
  • Interleukin-6 / blood
  • Male
  • Mice
  • Mice, SCID
  • Receptors, Interleukin-6 / immunology*
  • Rheumatoid Factor / blood
  • Synovial Membrane / immunology
  • Synovial Membrane / transplantation*

Substances

  • Antibodies, Monoclonal
  • Interleukin-6
  • Receptors, Interleukin-6
  • Rheumatoid Factor