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Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock.


ABSTRACT: Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects.To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock.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.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.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.

SUBMITTER: Wong HR 

PROVIDER: S-EPMC4098101 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Corticosteroids are associated with repression of adaptive immunity gene programs in pediatric septic shock.

Wong Hector R HR   Cvijanovich Natalie Z NZ   Allen Geoffrey L GL   Thomas Neal J NJ   Freishtat Robert J RJ   Anas Nick N   Meyer Keith K   Checchia Paul A PA   Weiss Scott L SL   Shanley Thomas P TP   Bigham Michael T MT   Banschbach Sharon S   Beckman Eileen E   Harmon Kelli K   Zimmerman Jerry J JJ  

American journal of respiratory and critical care medicine 20140401 8


<h4>Rationale</h4>Corticosteroids are prescribed commonly for patients with septic shock, but their use remains controversial and concerns remain regarding side effects.<h4>Objectives</h4>To determine the effect of adjunctive corticosteroids on the genomic response of pediatric septic shock.<h4>Methods</h4>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 microarr  ...[more]

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