Amelioration of arthritis in two murine models using antibodies to oncostatin M

Objective. Oncostatin M (OSM) is a member of the interleukin-6 cytokine fam ily, with well-documented effects on cell growth and differentiation. OSM a lso has proinflammatory and cartilage degradative properties. The aim of th is study was to investigate the significance of OSM in arthritis pathology using a neutralizing antibody in arthritis models. Methods. Collagen-induced arthritis (CIA) was established in male DBA/1 mic e. Reverse transcriptase-polymerase chain reaction was used to detect OSM m essenger RNA (mRNA) message levels in arthritic joints. Neutralizing anti-O SM antibody or control immunoglobulin was administered on days 1 and 3 afte r disease onset. Animals were assessed for clinical arthritis for 2 weeks, followed by a histologic analysis of paws. Pristane-induced arthritis (PIA) was produced in male CBA mice dosed with anti-OSM or control immunoglobuli n immediately before disease onset. Mice with PIA were assessed for clinica l arthritis over a period of 100 days. Results. Levels of mRNA for OSM, but not GAPDH, were elevated in arthritic joints of mice with CIA compared with those of normal controls. Mice with C IA treated with anti-OSM antibody showed significant amelioration of both t he clinical severity (P < 0.01) and the number of affected paws (P < 0.01) compared with control animals. Histologic analysis confirmed these clinical findings, revealing a marked reduction in cellular infiltration of synoviu m and cartilage damage. In the PIA model, the incidence of arthritis was 65 % in the control group compared with 0% in the anti-OSM-treated animals. Conclusion. These results demonstrate a key role for endogenously produced OSM as a potent mediator of joint pathology, and suggest that OSM might be a potentially important, novel therapeutic target for treatment of establis hed rheumatoid arthritis.