Open AccessSuppression of Collagen‐Induced Arthritis by Combination Cyclosporin a and Methotrexate Therapy
Author(s) -
Brahn Ernest,
Peacock Derek J.,
Banquerigo Mona Lisa
Publication year - 1991
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.1780341012
Subject(s) - methotrexate , medicine , arthritis , combination therapy , pharmacology , cancer research
Louvain (LOU) rats were administered either methotrexate (MTX; 0.3 mg/kg/week or 0.8 mg/kg/week intraperitoneally), cyclosporin A (CSA; 4 mg/kg/day or 10 mg/kg/day continuous infusion via osmotic pump), or a combination of both agents. The rats were immunized with native type II collagen (CII) to determine the effects of these agents on collagen‐induced arthritis, an animal model of rheumatoid arthritis. A significant decrease in the incidence ( P < 0.01) and severity of arthritis by clinical ( P < 0.05) and radiographic assessments ( P < 0.05) was found in recipients of combination therapy, compared with controls. Delayed‐type hypersensitivity reactions to CII were measured on day 26, and production of IgG antibody to CII was measured on days 7, 14, and 26. IgG antibody was evident by day 7, and titers were near‐maximal by day 14. Both delayed‐type hypersensitivity and antibodies to CII were reduced in animals that received the higher dosage of CSA. Liver, kidney, and spleen specimens obtained from rats treated with CSA and MTX demonstrated no histologic abnormalities on light microscopy, compared with controls. These studies indicate that CSA and MTX in combination is a safe and effective therapy for collagen‐induced arthritis and may be useful in the treatment of rheumatoid arthritis.