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

Abstract

Human monocytes (M phi) preexposed to cyclosporine (CsA) concentrations ranging between 1.0 and 10.0 micrograms/ml were impaired in their ability to stimulate autologous and allogeneic mixed lymphocyte reactions (MLR) when they were compared with control M phi unexposed to CsA. M phi preexposed to CsA and M phi preexposed to PGE2 displayed reduced expression of HLA-DR. Indomethacin protected M phi 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 phi membranes because decreases in the indirect light scattering properties of M phi were detected with the various CsA concentrations tested. Higher CsA concentrations significantly reduced the cellular volumes of M phi. The reductions of cellular volume were considerably less than the decreases in indirect light scatter. These data show that CsA interacts directly with M phi, 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.