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 cyclosporine and 4 novel immunosuppressive drugs on lymphocytes in whole blood collected from healthy cats.


METHODS
Whole blood samples collected from 10 healthy adult domestic shorthair cats.


METHODS
Mitogen-stimulated lymphocyte proliferation in whole blood incubated with and without various concentrations of cyclosporine, tacrolimus, sirolimus, mycophenolic acid (MPA), or A771726 was measured by use of [3H]thymidine incorporation. Drug concentrations that resulted in a 50% inhibition of mitogen-induced proliferation (IC50) were calculated. Lymphocyte viability was determined by use of the trypan blue dye exclusion method.


RESULTS
An obvious dose-response relationship for the antiproliferative effects of each drug was detected. Mean IC50 determined with concanavalin A was 46 nM for cyclosporine, 9 nM for tacrolimus, 12 nM for sirolimus, 16 nM for 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 for mycophenolic acid, and 25 mM for A771726. Mitogen-stimulated and nonstimulated lymphocytes remained viable, regardless of drug evaluated.


CONCLUSIONS
Tacrolimus, sirolimus, MPA, and A771726 inhibited in vitro mitogen-stimulated proliferation of feline lymphocytes in a dose-dependent manner. These novel immunosuppressive drugs may be useful for management of immune-mediated inflammatory diseases and prevention and treatment of rejection in cats that undergo organ transplantation.
Kyles
A E
AE
Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California, Davis 95616, USA.
Gregory
C R
CR
Craigmill
A L
AL
D000818:Animals; D002415:Cats / Q000276:immunology*; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D004396:Coloring Agents / Q000737:chemistry; D003208:Concanavalin A / Q000737:chemistry; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007555:Isoxazoles / Q000494:pharmacology; D000077339:Leflunomide; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D009173:Mycophenolic Acid / Q000494:pharmacology; D011043:Pokeweed Mitogens / Q000737:chemistry; D012588:Scintillation Counting / Q000662:veterinary; D020123:Sirolimus / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology; D014343:Trypan Blue / Q000737:chemistry
D004396:Coloring Agents; D007166:Immunosuppressive Agents; D007555:Isoxazoles; D011043:Pokeweed Mitogens; D003208:Concanavalin A; D016572:Cyclosporine; D000077339:Leflunomide; D009173:Mycophenolic Acid; D014343:Trypan Blue; D020123:Sirolimus; D016559:Tacrolimus