The impaired ability of human monocytes to stimulate autologous and allogeneic mixed lymphocyte reactions after exposure to cyclosporine. Associated alterations of HLA-DR expression and physical characteristics of monocytes.

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.