Effects of insulin on pharmacodynamics of immunosuppressive drugs against mitogen-activated human peripheral blood mononuclear cells

Abstract

Context: Diabetes mellitus is one of the most common causes of chronic renal failure. Immunosuppressive efficacies of glucocorticoids, calcineurin inhibitors, and mycophenolic acid are possibly affected by insulin after renal transplantation in these patients.Objectives: We investigated the effects of insulin on responses of mitogen-activated human peripheral blood mononuclear cells (PBMCs) to several immunosuppressive drugs.Materials and methods: Antiproliferative efficacies of prednisolone, hydrocortisone, cyclosporine, tacrolimus, and mycophenolic acid against concanavalin A-stimulated PBMCs were evaluated in the presence of physiological (5 μunits/mL) and super physiological (50 μunits/mL) concentrations of insulin. Insulin-receptor expressions on PBMCs were evaluated by flow cytometry.Results: Insulin itself had no effects on the mitogen-induced proliferation of PBMCs. The IC50 values of cyclosporine against the mitogen-activated PBMCs in the presence of 5 or 50 μunits/mL insulin were significantly higher than those of cyclosporine without insulin (p < 0.05). The IC50 values of mycophenolic acid significantly increased by 50 μunits/mL insulin (p < 0.01). Insulin receptors were detected on the mitogen-activated CD4+/CD14+ cells in PBMCs.Discussion and conclusions: These results indicate that insulin at even physiological concentration attenuates suppressive efficacies of several immunosuppressive drugs against mitogen-activated proliferation of human PBMCs, possibly via insulin receptors. Insulin used in dialysis patients accompanying diabetes mellitus is suggested to attenuate efficacies of immunosuppressive drugs after renal transplantation.