Use of the reversed passive Arthus reaction as a test for anti-inflammatory agents

The immune complex-induced reversed passive Arthus (RPA) reaction in the rabbit has been investigated as a screening test for detecting anti-inflammatory agents potentially more effective in the treatment of rheumatoid arthritis than those presently available. RPA lesions, characterized by edema, erythema, and hemorrhage, were elicited by intravenous injections of bovine serum albumin (BSA) followed by intradermal injections of rabbit anti-BSA antiserum. The anti-edema activities of compounds (mg quantities required for testing) were evaluated after their administration by the intradermal route (compounds admixed with antiserum) as well as by the intraperitoneal route. Of 14 reference anti-inflammatory agents tested by the intradermal screening procedure, only aurothioglucose and chloroquine were inactive. Other pharmacologically active compounds (e.g. antihistamines, anti-complement agents, cytotoxic-immunosuppressives) were also evaluated after their intradermal administration. Protoporphyrin, phloretin, and hexadimethrine bromide (Polybrene) were active. When whole antiserum, or the antibody fraction of the serum, was used to eliminate nonspecific edema, intraperitoneally administered reference agents were found to be effective in the RPA test.