title: Treatment of rheumatoid synovitis with anti-reshaping human interleukin-6 receptor monoclonal antibody: use of rheumatoid arthritis tissue implants in the SCID mouse model.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Sugitani, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Matsuno
authors.forename: T
authors.initials: T
authors.lastname: Sawai
authors.forename: T
authors.initials: T
authors.lastname: Nezuka
authors.forename: M
authors.initials: M
authors.lastname: Uzuki
authors.forename: H
authors.initials: H
authors.lastname: Tsuji
authors.forename: N
authors.initials: N
authors.lastname: Nishimoto
authors.forename: K
authors.initials: K
authors.lastname: Yoshizaki
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000915:Antibody Affinity; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000628:therapy*; D004195:Disease Models, Animal; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D051379:Mice; D016513:Mice, SCID; D019947:Receptors, Interleukin-6 / Q000276:immunology*; D012217:Rheumatoid Factor / Q000097:blood; D013583:Synovial Membrane / Q000276:immunology / Q000637:transplantation*
chemical_list: D000911:Antibodies, Monoclonal; D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D012217:Rheumatoid Factor