Prednisolone and cyclosporin A exert differential inhibitory effects on T-cell proliferation in vitro

To elucidate the mechanisms of action of prednisolone (pred) and cyclosporin A (CyA), we have investigated the effects of these immunosuppressive drugs on the proliferative response of human peripheral blood lymphocytes (PBMN) induced by various stimulants, well defined with regard to their monocyte dependence. We found that pred-induced inhibition of monocyte-dependent proliferative responses could be reversed by the addition of exogenous interleukin 2 (IL-2). Monocyte-independent proliferative responses were not affected by pred. These findings suggest that pred inhibits IL-2 production and subsequent lymphocyte proliferation at the level of the signal derived from the monocyte. In contrast, CyA inhibited monocyte-dependent as well as monocyte-independent proliferative responses of human PBMN. This inhibition could not be reversed by the addition of exogenous IL-2. We have previously demonstrated that CyA does not affect the expression of receptors for IL-2. Taken together, these data indicate that CyA-mediated inhibition does not primarily occur at the level of the IL-2 system, but rather affects the proliferative mechanism of the T cell itself. These data clearly demonstrate that pred and CyA act at distinct sites of the triggering process.