TREATMENT OF RHEUMATOID SYNOVITIS WITH ANTI-RESHAPING HUMAN INTERLEUKIN-6 RECEPTOR MONOCLONAL-ANTIBODY - USE OF RHEUMATOID-ARTHRITIS TISSUEIMPLANTS IN THE SCID MOUSE MODEL

Objective. To examine the effect of anti-reshaping human interleukin-6 receptor monoclonal antibody (anti-rsHuIL-6R mAb) on patients with rh eumatoid arthritis (RA), using SCID mice in which human RA synovial ti ssue has been grafted (SCID-HuRAg). Methods. Tissue from human RA pann us was implanted subcutaneously in the backs of 69 SCID mice, Differen ces from human RA were examined pathologically, Anti-rsHuIL-6R mAb (10 0 mu g) was administered intraperitoneally to mice once a week for 4 w eeks. 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-treat ed group, and an untreated group were used as controls. A total of 32 mice (8 in each group) were studied, Results. Histologic characteristi cs of the implanted tissues in SCID-HuRAg mice were very similar to th ose of human RA even 2 months after implantation. In addition, the pre sence of CD4-, CD8-, CD20-, IL-6-, tumor necrosis factor alpha-, tartr ate-resistant acid phosphatase (TRAP)-, matrix: metalloproteinase 1 (M MP-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-r sHuIL-6R mAb treatment group as compared with the control groups. Conc lusion. The SCID-HuRAg mouse is a useful model for evaluating the effe ctiveness of antirheumatic drugs. Anti-rsHuIL-6R mAb may have an antii nflammatory effect on RA synovitis and an inhibitory effect an osteocl asts.