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

Autor: Archer TM; Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, Mississippi., Mulligan C; Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, Mississippi., Narayanan L; Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, Mississippi., Riggs C; Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, Mississippi., Fellman C; Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, Mississippi.; Department of Clinical Sciences, Tufts University, North, MA., Thomason JM; Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, Mississippi., Wills RW; Department of Population and Preventative Medicine, College of Veterinary Medicine, Mississippi State University, Starkville, Mississippi., Boothe DM; Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama., Cruz-Espindola C; Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama., Harmon R; Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama., Mackin AJ; Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Starkville, Mississippi.
Jazyk: angličtina
Zdroj: Journal of veterinary internal medicine [J Vet Intern Med] 2020 May; Vol. 34 (3), pp. 1206-1213. Date of Electronic Publication: 2020 Feb 13.
DOI: 10.1111/jvim.15729
Abstrakt: 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.
(© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)
Databáze: MEDLINE
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