Effects of pharmacologic agents on the reversed passive Arthus reaction in the rat

Abstract

The Arthus reaction has many of the cardinal features of immune complex disease such as rheumatoid arthritis, i.e. immune complex formation, complemet fixation and neutrophil mediation. In an attempt to determine the usefulness of this experimental model in the search for new anti-arthritic drugs, the effects of drugs currently used for the treatment of rheumatologic diseases as well as various classes of pharmacologic agents on the RPA reaction in the rat were determined and compared with their effects on the carrageenan-induced edema and the passive anaphylaxis (PCA). Non-steriod anti-inflammatory drugs, i.e., indomethacin, phenylbutazone, sodium salicylate, sudoxicam; steriod, e .g. dexamethasone; and slow-acting antiarthritic agents, i.e. chloroquine, cyclophosphamine, myochrysine and D-penicillamine are either inactive or moderately active at extremely high doses. Antihistamine and antioseroyonin agents, i.e. mepyramine, methysergide and cyproheptadine that suppress the PCA reaction as well as agents that block release of mediators, i.e. disodium cromoglycate and diethylcarbamazine failed to influence the RPA reaction. Other pharmacologic agents includings MAO inhibitors, sedatives anticholinergics, fibrinolytic inhibitors, trypsin inhibitors, also showed no effect ont he RPA reaction. Of all compounds tested, colchicine is most potent in suppressing the RPA reaction. It is concluded that the RPA reaction in the rat appears to be a useful model in uncovering anti-inflammatory agents that act modulating functions of polymorphonuclear leukocytes.