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

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-gamma). 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-gamma 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] Delta Ct) and IFN-gamma (2.33 [1.66-3.00 Delta Ct]) values were significantly lower (bothP < .001) than values after treatment (10.75 [10.16-11.34] and 10.79 [10.11-11.46] Delta Ct, respectively) with cyclosporine. Similarly, least squares means before treatment for IL-2 (1.55 [1.07-2.02] Delta Ct) and IFN-gamma (2.62 [2.32-2.92] Delta Ct) values were significantly lower (bothP < .001) than values after treatment (3.55 [3.06-4.00] and 5.22 [4.92-5.52] Delta Ct, respectively) with prednisone. Comparing delta cycle threshold values after treatment among drugs, cyclosporine was significantly different than prednisone (IL-2 and IFN-gamma bothP < .001), with cyclosporine more suppressive than prednisone. Conclusions and Clinical Importance Prednisone and cyclosporine both affected expression of IL-2 and IFN-gamma, suggesting that both have the ability to influence results when utilizing pharmacodynamic monitoring of cyclosporine treatment.