Study was performed at the Mississippi State University College of Veterinary Medicine.
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Standard Article
Pharmacodynamic Monitoring of Canine T-Cell Cytokine Responses to Oral Cyclosporine
Article first published online: 28 SEP 2011
DOI: 10.1111/j.1939-1676.2011.00797.x
Copyright © 2011 by the American College of Veterinary Internal Medicine
Issue
Journal of Veterinary Internal Medicine
Volume 25, Issue 6, pages 1391–1397, November-December 2011
Additional Information
How to Cite
Archer, T.M., Fellman, C.L., Stokes, J.V., Pinchuk, L.M., Lunsford, K.V., Pruett, S.B., Langston, V.C. and Mackin, A.J. (2011), Pharmacodynamic Monitoring of Canine T-Cell Cytokine Responses to Oral Cyclosporine. Journal of Veterinary Internal Medicine, 25: 1391–1397. doi: 10.1111/j.1939-1676.2011.00797.x
Study was presented as an abstract at the 2010 ACVIM Forum in Anaheim, California (Abstract #122).
Publication History
- Issue published online: 16 NOV 2011
- Article first published online: 28 SEP 2011
- Manuscript Accepted: 9 AUG 2011
- Manuscript Revised: 1 JUL 2011
- Manuscript Received: 4 FEB 2011
- Abstract
- Article
- References
- Cited By
Keywords:
- Flow cytometry;
- Interferon-gamma;
- Interleukin-2;
- Interleukin-4
Background
Pharmacodynamic assays measure the immunosuppressive effects of cyclosporine on T-cells and offer an alternative assessment of efficacy in individual patients.
Objective
To assess the immunosuppressive effects of high and low dosage cyclosporine on canine T-cells and to develop a novel testing system for individualized dose adjustment.
Animals
Seven healthy female Walker hounds.
Methods
Experimental study using a paired comparison design. Flow cytometry was used to measure T-cell expression of IL-2, IL-4, and IFN-γ. Cytokine expression 8 days after oral administration of high and low dosages of cyclosporine was compared to baseline and washout values, respectively. The high dosage was initially 10 mg/kg q12h and was then adjusted to attain established immunosuppressive trough blood drug concentrations (>600 ng/mL). The low dosage was 5 mg/kg q24h.
Results
High dosage cyclosporine resulted in significant decreases in IL-2 and IFN-γ expression (P = .0156, P = .0156), but not IL-4 expression (P = .2188). Low dosage cyclosporine was associated with a significant decrease in IFN-γ expression (P = .0156), while IL-2 expression was not affected (P = .1094).
Conclusions and Clinical Importance
T-cell function is suppressed at trough blood drug concentrations exceeding 600 ng/mL, and is at least partially suppressed in some dogs at low dosages. Direct evaluation of T-cell function could be an effective, more sensitive alternative to measuring blood drug concentrations for monitoring immunosuppressive therapy.