THE IMPAIRED ABILITY OF HUMAN MONOCYTES TO STIMULATE AUTOLOGOUS AND ALLOGENEIC MIXED LYMPHOCYTE REACTIONS AFTER EXPOSURE TO CYCLOSPORINE

Abstract

Human monocytes (M.vphi.) preexposed to cyclosporine (CsA) concentrations ranging between 1.0 and 10.0 .mu.g/ml were impaired in their ability to stimulate autologous and allogeneic mixed lymphocyte reactions (MLR) when they were compared with control M.vphi. unexposed to CsA. M.vphi. preexposed to CsA and M.vphi. preexposed to PGE2 [prostaglandin E2] displayed reduced expression of HLA-DR. Indomethacin protected M.vphi. from decreased HLA-DR expression at lower CsA concentrations, but was unable to prevent the decrease of HLA-DR with higher concentrations of CsA. CsA appeared capable of perturbing M.vphi. membranes because decreases in the indirect light scattering properties of M.vphi. were detected with the various CsA concentrations tested. Higher CsA concentration significantly reduced the cellular volumes of M.vphi.. The reductions of cellular volume were considerably less than the decreases in indirect light scatter. CsA interacts directly with M.vphi. reducing their functional ability to trigger MLR responses and their phenotypic expression of HLA-DR. The decreased HLA-DR expression is mediated via prostaglandins at low CsA concentrations and the decreased HLA-DR expression is mediated via membrane perturbations unrelated to prostaglandins at high CsA concentrations.