title: Pharmacodynamic monitoring of canine T-cell cytokine responses to oral cyclosporine.
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.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA. tarcher@cvm.msstate.edu
authors.forename: T M
authors.initials: TM
authors.lastname: Archer
authors.forename: C L
authors.initials: CL
authors.lastname: Fellman
authors.forename: J V
authors.initials: JV
authors.lastname: Stokes
authors.forename: L M
authors.initials: LM
authors.lastname: Pinchuk
authors.forename: K V
authors.initials: KV
authors.lastname: Lunsford
authors.forename: S B
authors.initials: SB
authors.lastname: Pruett
authors.forename: V C
authors.initials: VC
authors.lastname: Langston
authors.forename: A J
authors.initials: AJ
authors.lastname: Mackin
mesh_terms: D000284:Administration, Oral; D000818:Animals; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D007166:Immunosuppressive Agents; D007376:Interleukin-2; D007371:Interferon-gamma; D016572:Cyclosporine