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

Am J Vet Res. 2000 Aug;61(8):906-9. doi: 10.2460/ajvr.2000.61.906.


Objective: To compare the in vitro immunosuppressive effects of cyclosporine and 4 novel immunosuppressive drugs on lymphocytes in whole blood collected from healthy cats.

Sample population: Whole blood samples collected from 10 healthy adult domestic shorthair cats.

Procedure: 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 and clinical relevance: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cats / immunology*
  • Cell Division / drug effects
  • Cell Division / immunology
  • Coloring Agents / chemistry
  • Concanavalin A / chemistry
  • Cyclosporine / pharmacology
  • Dose-Response Relationship, Drug
  • Immunosuppressive Agents / pharmacology*
  • Inhibitory Concentration 50
  • Isoxazoles / pharmacology
  • Leflunomide
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Activation / immunology
  • Mycophenolic Acid / pharmacology
  • Pokeweed Mitogens / chemistry
  • Scintillation Counting / veterinary
  • Sirolimus / pharmacology
  • Tacrolimus / pharmacology
  • Trypan Blue / chemistry


  • Coloring Agents
  • Immunosuppressive Agents
  • Isoxazoles
  • Pokeweed Mitogens
  • Concanavalin A
  • Cyclosporine
  • Leflunomide
  • Mycophenolic Acid
  • Trypan Blue
  • Sirolimus
  • Tacrolimus