Comparison of the in vitro antiproliferative effects of five immunosuppressive drugs on lymphocytes in whole blood from cats

Objective - To compare the in vitro immunosuppressive effects of cyclospori ne and 4 novel immunosuppressive drugs on lymphocytes in whole blood collec ted from healthy cats. Sample Population - Whole blood samples collected from 10 healthy adult dom estic shorthair cats. Procedure - Mitogen-stimulated lymphocyte proliferation in whole blood incu bated with and without various concentrations of cyclosporine, tacrolimus, sirolimus, mycophenolic acid (MPA), or A771726 was measured by use of [H-3] thymidine incorporation. Drug concentrations that resulted in a 50% inhibit ion of mitogen-induced proliferation (IC50) were calculated, Lymphocyte via bility was determined by use of the trypan blue dye exclusion method. Results-An obvious dose-response relationship for the antiproliferative eff ects of each drug was detected. Mean IC50 determined with concanavalin A wa s 46 nM for cyclosporine, 9 nM for tacrolimus, 12 nM for sirolimus, 16 nM f or MPA, and 30 mM for A771726, whereas with pokeweed mitogen, mean IC50 was 33 nM for cyclosporine, 5 nM for tacrolimus, 15 nM for sirolimus, 14 nM fo r mycophenolic acid, and 25 mM for A771726. Mitogen-stimulated and nonstimu lated lymphocytes remained viable, regardless of drug evaluated. Conclusions and Clinical Relevance - Tacrolimus, sirolimus, MPA, and A77172 6 inhibited in vitro mitogen-stimulated proliferation of feline lymphocytes in a dose-dependent manner. These novel immunosuppressive drugs may be use ful for management of immune-mediated inflammatory diseases and prevention and treatment of rejection in cats that undergo organ transplantation.