title: Ex vivo stimulation of whole blood as a means to determine glucocorticoid sensitivity.
abstract: OBJECTIVE
  Glucocorticoids are commonly prescribed to treat a number of diseases including the majority of inflammatory diseases. Despite considerable interpersonal variability in response to glucocorticoids, an insensitivity rate of about 30%, and the risk of adverse side effects of glucocorticoid therapy, currently no assay is performed to determine sensitivity.
  
  
  METHODS
  Here we propose a whole blood ex vivo stimulation assay to interrogate known glucocorticoid receptor (GR) up- and downregulated genes to indicate glucocorticoid sensitivity. We have chosen to employ real-time PCR in order to provide a relatively fast and inexpensive assay.
  
  
  RESULTS
  We show that the GR-regulated genes, GILZ and FKBP51, are upregulated in whole blood by treatment with dexamethasone and that LPS-induction of cytokines (IL-6 and TNFα) are repressed by dexamethasone in a dose responsive manner. There is considerable interpersonal variability in the maximum induction of these genes but little variation in the EC(50) and IC(50) concentrations. The regulation of the GR-induced genes differs throughout the day whereas the suppression of LPS-induced cytokines is not as sensitive to time of day.
  
  
  CONCLUSIONS
  In all, this assay would provide a method to determine glucocorticoid receptor responsiveness in whole blood.
authors.affiliation: Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Burnsides
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Corry
authors.forename: Jacob
authors.initials: J
authors.lastname: Alexander
authors.forename: Catherine
authors.initials: C
authors.lastname: Balint
authors.forename: David
authors.initials: D
authors.lastname: Cosmar
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
authors.forename: Jeanette I Webster
authors.initials: JI
authors.lastname: Marketon