MTX affects inflammation and tissue destruction differently in the rat AA model

Objective, To investigate the dose response relationships of methotrexate ( MTX) therapy in rat adjuvant arthritis (AA), an animal model of rheumatoid arthritis (RA). Methods. Female Lewis rats were fed a defined diet and were treated with 0, 0.3, 1, 2, 3, 5, and 10 mg MTX per week beginning 3 days after adjuvant in jection and lasting 6 weeks, The presence or absence of arthritis, and its degree were measured by hindpaw edema scores, ankle widths, and radiographi c and histopathologic scores. Results, The 2, 3, 5, and 10 mg MTX per week doses resulted in deaths befor e the end of the protocol and suppressed normal body weight gain. Tissue de struction. measured by radiographic and histopathologic scores, was reduced in a dose dependent manner with increasing MTX dose. Suppression of inflam mation, measured by ankle widths and radiographic and histopathologic score s, reached a maximum at the 1 mg MTX dose and declined at higher doses. Conclusions. Suppression of tissue destruction and inflammation in rat AA d oes not occur in a concerted fashion as the dose of MTX increases. The impl ications of these findings to human disease remain to be determined.