Abstract

Various parameters in the adjuvant arthritic rat model were investigated for their pharmacologic sensitivity and specificity. Secondary (immune) inflammation and serum lysozyme activity were the most sensitive parameters in detecting anti-inflammatory and immunosuppressive activity. In contrast to anti-inflammatory agents, immunosuppressive agents did not alter the primary (nonimmune) inflammation and did not decrease the severity of secondary inflammation when administered therapeutically. Immunosuppression in the adjuvant arthritic rat model was also detected by depression of hemagglutinin titers. Several agents which are not clinically established anti-inflammatory drugs but which have been reported to elicit anti-inflammatory activity in other experimental models were not effective in decreasing the primary and/or secondary inflammation of adjuvant arthritis. However, certain "nonspecific" agents from various pharmacologic classes were effective in suppressing secondary inflammation. In contrast to anti-inflammatory and immunosuppressive agents, however, these nonspecific agents did not suppress the increase in serum lysozyme activity and/or aggravated adjuvant-induced body weight loss. The results suggest that adjuvant arthritis is a sensitive model, with improved specificity, to detect both anti-inflammatory and immunosuppressive agents. The utilization of immune and nonimmune inflammation, antibody titers, serum lysozyme, body weight changes and various dosing regimens in the adjuvant arthritic rat model aids in elucidating the mechanisms and therapeutic potential of antiarthritic agents.