SUPPRESSION OF HUMAN CYTOTOXIC LYMPHOCYTES BY METHYLPREDNISOLONE

Abstract

To gain insight into the immunosuppressive mechanism of action of corticosteroids, an in vitro model of the cellular immune response was used to study the effect of methylprednisolone on human lymphocyte-mediated cytotoxicity. Concentrations from 0.25-10 .mu.g/ml were equally effective in producing 74% suppression of lymphocyte-mediated cytotoxicity when the steroid was present during the entire period of in vitro sensitization. A 12.5-fold increase in effector to target cell ratio was required to achieve 30% 51Cr release when cytotoxic lymphocytes were generated in the presence of methylprednisolone. Lymphocyte-mediated cytotoxicity was suppressed 48% when methylprednisolone was present only during the initial 24 h of the 7-day in vitro sensitization period. Methylprednisolone also effective inhibited cytotoxicity when it was incubated with sensitized lymphocytes for 3 h before incubating these cells with target cells. Two of the major immunosuppressive mechanisms of action of methylprednisolone may be suppression of the generation of the cytotoxic lymphocytes and suppression of specifically sensitized cytotoxic lymphocytes.