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J Vet Intern Med. 2011 Nov-Dec;25(6):1391-7. doi: 10.1111/j.1939-1676.2011.00797.x. Epub 2011 Sep 28.

Pharmacodynamic monitoring of canine T-cell cytokine responses to oral cyclosporine.

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1
Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA. tarcher@cvm.msstate.edu

Abstract

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.

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