Effects of antiarthritic compounds on sheep erythrocyte-induced delayed-type hypersensitivity

Delayed hypersensitivity (DTH) to sheep erythrocytes (SRBC) in mice is a simple model of cellular immunity mediated primarily by Ly 1+ T-cells. Because little is known about the pharmacology of this model, the therapeutic effects of a variety of antiarthritic agents were tested. Swelling was determined using mercury plethysmography and used to determine drug activity. Two immunosuppressive agents (cyclophosphamide and azathioprine) and two steroids (dexamethasone and hydrocortisone) significantly reduced swelling. Only one of six nonsteroidal antiinflammatory drugs (NSAIDs), aspirin, reduced swelling. Indomethacin, phenylbutazone, and benoxaprofen augmented swelling and ibuprofen and isoxicam were inactive. Four disease-modifying antirheumatic drugs (DMARDs), D-penicillamine, levamisole, chloroquine, and aurothioglucose, were tested and none inhibited swelling. Aurothioglucose significantly augmented swelling. In conclusion, only steroids and immunosuppressive agents had consistent effects on DTH to SRBC. In general, NSAIDs and DMARDs were either inactive or augmented swelling. These results suggest that this model may be of use as a routine screen for immunomodulatory agents.