Suppression of human cytotoxic lymphocytes by methylprednisolone. An immunosuppressive mechanism of action of steroids

Abstract

In order to gain insight into the immunosuppresive 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 to 10 microgram/ml were equally effective in producing 74% suppression 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 prescence of methylprednisolone. Lymphocyte-mediated cytotoxicity was suppressed 48% when methylprednisolone was present only during the initial 24 hr of the 7-day in vitro sensitization period. Methylprednisolone also effectively inhibited cytotoxicity when it was incubated with sensitized lymphocytes for 3hr before incubating these cells with target cells. Our observations suggest that two of the major immunosuppressive mechanisms of action methylprednisolone are suppression of the generation of cytotoxic lymphocytes and suppression of specifically sensitized cytotoxic lymphocytes.