Open AccessTreatment of rheumatoid synovitis with anti‐reshaping human interleukin‐6 receptor monoclonal antibody: Use of rheumatoid arthritis tissue implants in the SCID mouse model
Author(s) -
Matsuno H.,
Sawai T.,
Nezuka T.,
Uzuki M.,
Tsuji H.,
Nishimoto N.,
Yoshizaki K.
Publication year - 1998
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(199811)41:11<2014::aid-art17>3.0.co;2-t
Subject(s) - synovitis , medicine , rheumatoid arthritis , monoclonal antibody , immunohistochemistry , pathology , arthritis , tumor necrosis factor alpha , immunology , antibody
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 µg) 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 α‐, 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 effects on RA synovitis and an inhibitory effect on osteoclasts.