Effects of oral administration of 5 immunosuppressive agents on activated T-cell cytokine expression in healthy dogs

Abstract

Background: Dogs are often adminstered >1 immunosuppressive medication when treating immune-mediated diseases, and determining whether these different medications affect IL-2 expression would be useful when performing pharmacodynamic monitoring during cyclosporine therapy. Hypothesis/Objectives: To determine the effects of 5 medications (prednisone, cyclosporine, azathioprine, mycophenolate mofetil, and leflunomide) on activated T-cell expression of the cytokines IL-2 and interferon-gamma (IFN-γ). Animals: Eight healthy dogs. Methods: Randomized, cross-over study comparing values before and after treatment, and comparing values after treatment among drugs. Dogs were administered each drug at standard oral doses for 1 week, with a washout of at least 21 days. Activated T-cell expression of IL-2 and IFN-γ mRNA was measured by quantitative reverse transcription polymerase chain reaction. Blood drug concentrations were measured for cyclosporine, mycophenolate, and leflunomide metabolites. Results: Least squares means (with 95% confidence interval) before treatment for IL-2 (2.91 [2.32-3.50] ΔCt) and IFN-γ (2.33 [1.66-3.00 ΔCt]) values were significantly lower (both P