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

Abstract

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

Keywords

• azathioprine
• cyclosporine
• interferon gamma
• interleukin 2
• leflunomide
• mycophenolate mofetil