Inhibition of the primary lesion of adjuvant. induced polyarthritis in rats (18-hour arthritis test) for specific detection of clinically effective anti-arthritic drugs.

Adjuvant-induced polyarthritis can be induced in rats 14 to 21 days after subplantar injection of 0.1 ml of a 0.5% suspension of Mycobacterium tuberculosis in heavy mineral oil into a hind paw. However, edema volume of the injected pay (primary lesion) developed rapidly and reached a peak in 18 hours after injection and persisted at this level for up to 90 hours. A single oral dose of 25 clinically effective or experimental antiarthritic agents given 1 hour prior to M. tuberculosis injection and tested 18 hours later significantly inhibited edema formation in a dose-related fashion. Only D-penicillamine and azathioprine which are clinically effected, gave false-negative responses in this test. However, cyclophosphamide, another immunosuppressive like azathioprine, was effective. The ED50 values for most drugs in this test were at least 2-fold greater than in the carrageenan edema test. On the other hand, of the 17 drugs considered as false-positives in the carrageenan test only the antihistaminic agent, chlorpheniramine maleate, was effective in the 18-hour arthritis test, whereas several other agents with this activity but different chemical structure proved ineffective. In addition, 18 other agents from various classes of therapeutic agents were also tested and found ineffective in each test. These data suggest that the 18-hour arthritis test in rats is highly specific and a more reliable screening procedure than carrageenan-induced edema for detecting potentially useful antiarthritic agents. The practical advantages of this method are also discussed.