Lymphocyte suppression by glucocorticoids with cyclosporine, tacrolimus, pentoxifylline, and mycophenolic acid

Methylprednisolone has been found to be significantly more suppressive than prednisolone (the pharmacologically active metabolite of prednisone) of mitogen-stimulated human lymphocyte proliferation. In this study, peripheral blood mononuclear cells (PBMC) from end stage renal disease patients were cultured with phytohemagglutinin (PHA) alone and with methylprednisolone and prednisolone individually, as well as each glucocorticoid (10(-7) mol/L) in combination with 300 ng/ml cyclosporine, 10 ng/ml tacrolimus, 25 microg/ml pentoxifylline, and 10(-7) mol/L mycophenolic acid. Under each experimental condition, the mean +/- SD % inhibition of PHA-stimulated 3H-thymidine incorporation was significantly greater with methylprednisolone than with prednisolone: methylprednisolone 55 +/- 17 versus prednisolone 28 +/- 14, p < 0.001; methylprednisolone + cyclosporine 76 +/- 18 versus prednisolone + cyclosporine 52 +/- 18, p < 0.001; methylprednisolone + tacrolimus 74 +/- 18 versus prednisolone + tacrolimus 50 +/- 20, p = 0.001; methylprednisolone + mycophenolic acid 69 +/- 14 versus prednisolone + mycophenolic acid 46 +/- 15, p < 0.001. These results confirm and extend previous observations and suggest that methylprednisolone might be more effective than prednisone in treatment protocols used to suppress allograft rejection.