Pharmacodynamic Monitoring of Canine T‐Cell Cytokine Responses to Oral Cyclosporine

Journal of Veterinary Internal Medicine

T.M. Archer²  C.L. Fellman²  J.V. Stokes¹  L.M. Pinchuk¹  K.V. Lunsford²  S.B. Pruett¹  V.C. Langston² 

[1] Department of Basic Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS;Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS

关键词: Flow cytometry;    Interferon‐gamma;    Interleukin‐2;    Interleukin‐4;   

DOI  :  10.1111/j.1939-1676.2011.00797.x

来源: Wiley

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2011 by the American College of Veterinary Internal Medicine