title: Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock.
abstract: BACKGROUND
  Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects.
  
  
  OBJECTIVE
  To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock.
  
  
  METHODS
  We retrospectively analyzed an existing transcriptomic database of pediatric septic shock. Subjects receiving any formulation of systemic corticosteroids at the time of blood draw for microarray analysis were classified in the septic shock corticosteroid group. We compared normal control subjects (n = 52), a septic shock no corticosteroid group (n = 110), and a septic shock corticosteroid group (n = 70) using analysis of variance. Genes differentially regulated between the no corticosteroid group and the corticosteroid group were analyzed using Ingenuity Pathway Analysis.
  
  
  RESULTS
  The two study groups did not differ with respect to illness severity, organ failure burden, mortality, or mortality risk. There were 319 gene probes differentially regulated between the no corticosteroid group and the corticosteroid group. These genes corresponded predominately to adaptive immunity-related signaling pathways, and were down-regulated relative to control subjects. Notably, the degree of down-regulation was significantly greater in the corticosteroid group, compared with the no corticosteroid group. A similar pattern was observed for genes corresponding to the glucocorticoid receptor signaling pathway.
  
  
  CONCLUSIONS
  Administration of corticosteroids in pediatric septic shock is associated with additional repression of genes corresponding to adaptive immunity. These data should be taken into account when considering the benefit to risk ratio of adjunctive corticosteroids for septic shock.
authors.affiliation: 1 Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Hector R
authors.initials: HR
authors.lastname: Wong
authors.forename: Natalie Z
authors.initials: NZ
authors.lastname: Cvijanovich
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Allen
authors.forename: Neal J
authors.initials: NJ
authors.lastname: Thomas
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Freishtat
authors.forename: Nick
authors.initials: N
authors.lastname: Anas
authors.forename: Keith
authors.initials: K
authors.lastname: Meyer
authors.forename: Paul A
authors.initials: PA
authors.lastname: Checchia
authors.forename: Scott L
authors.initials: SL
authors.lastname: Weiss
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Shanley
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bigham
authors.forename: Sharon
authors.initials: S
authors.lastname: Banschbach
authors.forename: Eileen
authors.initials: E
authors.lastname: Beckman
authors.forename: Kelli
authors.initials: K
authors.lastname: Harmon
authors.forename: Jerry J
authors.initials: JJ
authors.lastname: Zimmerman
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D015894:Genome, Human; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007223:Infant; D015278:Intensive Care Units, Pediatric; D007958:Leukocyte Count; D008297:Male; D012189:Retrospective Studies; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D015398:Signal Transduction; D046888:Tissue Array Analysis
chemical_list: D005938:Glucocorticoids