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

• Published in: Arthritis and rheumatism Vol. 44; no. 11; pp. 2697 - 2702
• Main Authors: Plater‐Zyberk, C., Buckton, J., Thompson, S., Spaull, J., Zanders, E., Papworth, J., Life, P. F.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01.11.2001; Wiley
• Subjects: Animals; Antibodies - therapeutic use; Arthritis, Experimental - chemically induced; Arthritis, Experimental - drug therapy; Arthritis, Experimental - pathology; Bacterial Proteins; Biological and medical sciences; Chaperonin 60; Chaperonins - pharmacology; Collagen - immunology; Collagen - pharmacology; Disease Models, Animal; Diseases of the osteoarticular system; DNA Primers - chemistry; Edema - drug therapy; Glyceraldehyde-3-Phosphate Dehydrogenases - genetics; Glyceraldehyde-3-Phosphate Dehydrogenases - immunology; Glyceraldehyde-3-Phosphate Dehydrogenases - metabolism; Immunoglobulin G - administration & dosage; Inflammatory joint diseases; Joints - chemistry; Joints - drug effects; Joints - metabolism; Joints - pathology; Male; Medical sciences; Mice; Mice, Inbred CBA; Mice, Inbred DBA; Oncostatin M; Peptides - genetics; Peptides - immunology; Peptides - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Terpenes - immunology; Terpenes - pharmacology; Animal model; Pathogenesis; Diseases of the osteoarticular system; Reverse transcription; Autoimmune disease; Inflammatory joint disease; Arthritis; Histopathology; Messenger RNA; Medical application; Immunopathology; Immune response; Antibody; Rodentia; Inflammation; Experimental study; Gene expression; Oncostatin M; Polymerase chain reaction; Vertebrata; Chronic; Mammalia; Treatment; Mouse; Collagen; Rheumatoid arthritis; Molecular biology
• ISSN: 0004-3591; 1529-0131
• DOI: 10.1002/1529-0131(200111)44:11<2697::AID-ART450>3.0.CO;2-#

Objective Oncostatin M (OSM) is a member of the interleukin‐6 cytokine family, with well‐documented effects on cell growth and differentiation. OSM also has proinflammatory and cartilage degradative properties. The aim of this 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 mice. Reverse transcriptase–polymerase chain reaction was used to detect OSM messenger RNA (mRNA) message levels in arthritic joints. Neutralizing anti‐OSM antibody or control immunoglobulin was administered on days 1 and 3 after 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 immunoglobulin immediately before disease onset. Mice with PIA were assessed for clinical 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 CIA treated with anti‐OSM antibody showed significant amelioration of both the 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 synovium 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 established rheumatoid arthritis.