Studies on the effects of pharmacological agents on antigen-induced arthritis in BALB/c mice.

The model of antigen-induced monoarticular arthritis in BALB/c mice, originally described by Brackertz et al. (1), has been examined with regard to disease pathogenesis and the activities of established antirheumatic agents. The acute phase of the arthritis, up to 7 days after intra-articular (IA) challenge, was characterized by intense polymorphonuclear leukocyte infiltration into the challenged joint, synovial lining cell hypertrophy and hyperplasia, accumulation of mononuclear cells within the subsynovial tissue, and pannus formation. Erosions of articular cartilage and bone commenced 7-14 days after IA challenge and progressed with time. Chronic synovitis was still evident 56 days after IA challenge. Prednisolone at 1 and 5 mg/kg, when administered against an established arthritis (dosing days 14-42), suppressed the histopathological changes. A similar level of suppression was observed when prednisolone was administered from days 0-42, indicating that the drug had no additional effect on the development phase of the arthritis. The non-steroidal anti-inflammatory agents (NSAIAs) indomethacin, ibuprofen and flurbiprofen failed to suppress either the established or developing disease. Daily treatment with D-penicillamine, tiopronin or chloroquine on days 14-42 had no significant effect on the arthritis; treatment with either D-penicillamine or chloroquine on days 0-56 was also ineffective. When administered on days 14-42 or 0-42 neither gold thiomalate nor auranofin were able to suppress the erosive changes. Sulphasalazine (10-30 mg/kg) suppressed the arthritis whereas sulphapyridine was inactive. Azathioprine (20 mg/kg) suppressed the erosive changes when administered over days 14-42 or 0-42; this activity was associated with toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)