Combination effect of Bucillamine and Methotrexate on rat type II collagen-induced arthritis model

Purpose: To expect disease-modified anti-rheumatic drugs (DMARDs) combination therapy on rheumatoid arthritis (RA), combination effect of bucillamine (Buc) and methotrexate (MTX) on type II collagen-induced arthritis model (CIA) was investigated. IgM production from B lymphocytes was examined to understand one of the mechanisms of combination effects. Methods: Rat CIA was induced by bovine type II collagen (CII) sensitization. Buc 3 mg/kg was orally administrated once daily for 21 days from the day of sensitization. MTX 0.2 mg/kg was orally administrated on three times a week for three weeks as the mimic of the clinical dose. IgM production from B lymphocytes was examined with the stimulation of IL-2 and Staphylococcus aureus, and Buc or MTX were treated in vitro. Results: Buc and MTX combination additively reduced the hind paw swelling and bone destruction in CIA. α1-acidic glycoprotein, one of the inflammation markers in serum, and anti-CII antibody titer were also decreased. Buc and MTX combination additively reduced Staphylococcus aureus and IL-2 induced IgM production from B lymphocytes in vitro. Conclusion: This study provides the first evidence that Buc exerts additive effect with MTX in CIA rats. Regulating B cell function by Buc and MTX may contribute to their additive effects on rat CIA to some degree.