Pharmacological aspects of arthritis induced by a muramyl dipeptide analogue in rats

Fourteen consecutive daily subcutaneous injections of 4 mg/kg of the muramyl dipeptide analogue MDP-Lys(L18) into rats caused arthritis characterized by swelling of the tarsal joint, increases in lymphocytes and monocytes in the peripheral blood, and elevated serum immunoglobulin G (IgG). The present study was performed to evaluate the effects of indomethacin, phenylbutazone, dexamethasone, D-penicillamine, aurothioglucose, cyclophosphamide and cyclosporin A on this arthritis. Administration of indomethacin, phenylbutazone or dexamethasone inhibited the development of the tarsal joint swelling, suggesting that prostaglandins may be involved in the pathogenesis of the arthritis. Cyclophosphamide reduced the arthritis, together with decreases in the lymphocyte count and the serum IgG level. Cyclosporin A worsened the arthritis in a dose-dependent manner and increased the neutrophil count without raising the serum IgG level, but inhibited the induction of adjuvant arthritis in rats with Mycobacterium bacilli. MDP-Lys(L18) may therefore induce arthritis differing in mechanism from adjuvant arthritis.