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

• Published in: Immunopharmacology and immunotoxicology 2016-09, Vol.38 (5), p.372-378
• Main Authors: Chen, Shuiling, Sugiyama, Kentaro, Inamura, Mariko, Tanaka, Sachiko, Onda, Kenji, Yin, Huijun, Hirano, Toshihiko
• Format: Article
• Language: English
• Subjects: Cell Proliferation - drug effects; Female; Humans; Immunosuppressive Agents - pharmacokinetics; Immunosuppressive Agents - pharmacology; Insulin; Insulin - pharmacology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - pathology; Male; Mitogens - pharmacology; peripheral blood mononuclear cells; pharmacodynamics of immunosuppressive drugs; renal transplantation; T-cell mitogen
• ISSN: 0892-3973; 1532-2513
• DOI: 10.1080/08923973.2016.1214143

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 IC 50 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