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

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Abstract
Background Dogs are often adminstered >1 immunosuppressive medication when treating immune‐mediated diseases. 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. Dogs were administered each drug 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. Drug concentrations in blood 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.
Funding Information
  • Dr. Hugh G. Ward Endowment Chair
  • Mississippi State University College of Veterinary Medicine Internal Competitive Research Grant
  • Dr. Hugh G. Ward Endowment Chair
  • Mississippi State University College of Veterinary Medicine Internal Competitive Research Grant

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