Different effect of cyclosporin A on arthritides induced by a muramyl dipeptide analogue or the complete adjuvant in rats.

Muramyl dipeptide-Lys (L18) given by daily subcutaneous infjection for 14 days induced arthritis in male Lewis, Fischer and nude rats, to a lesser degree in the last two than in the first strain. On the other hand, a single intradermal administration of Freund's complete adjuvant induced arthritis in Lewis and Fishcher but not nude rats. Cyclosporin A(CsA) co-administered for 14 days markedly exacerbated the muramyl dipeptide-Lys(L18) induced arthritis (MIA) in rats of all three strains, but completely blocked the development of the adjuvant induced arthritis (AIA) in Lewis rats. Furthermore, AIA was transferred to recipient Lewis rats through spleen cells obtained from the donors with AIA, whereas MIA was not. Antibodies against type II collagen and DNA were not detected in sera from MIA or AIA rats. These data show a clear difference between MIA and AIA in the pattern of development of arthritis and suggest that delayed hypersensitivity reactions may be involved in the pathogenetic mechanisms of AIA, but not in MIA