Effects of oral administration of 5 immunosuppressive agents on activated T‐cell cytokine expression in healthy dogs. (13th February 2020)

• Record Type: Journal Article
• Authors: Archer, Todd M.; Mulligan, Charlee; Narayanan, Lakshmi; Riggs, Caitlin; Fellman, Claire; Thomason, John M.; Wills, Robert W.; Boothe, Dawn M.; Cruz‐Espindola, Crisanta; Harmon, Roy; Mackin, Andrew J.
• Is Part Of: Journal of veterinary internal medicine. Volume 34:Number 3(2020)
• Page Start: 1206
• Page End: 1213
• Publication Date: 2020-02-13
• Subjects: azathioprine -- cyclosporine -- interferon gamma -- interleukin 2 -- leflunomide -- mycophenolate mofetil -- prednisone [Correction added on March 16, 2020, after first online publication: See Appendix S1 for correction details.]; Veterinary medicine -- Periodicals; 636.0896
• DOI: 10.1111/jvim.15729
• Languages: English
• ISSNs: 0891-6640

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.