Transcriptomics,Genomics

Dataset Information

29

Prospective randomized doubleblind assessment of transcriptome modulation by hydrocortisone in severe burn shock


ABSTRACT: Rationale: Despite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm on the immune system. Few studies assessed hydrocortisone impact on the transcriptional response in shock, and we are lacking data in burns. Objectives: To assess the hydrocortisone-induced transcriptional modulation in severe burn shock, particularly on the immune response. Methods: We collected whole blood samples (n= 117) during a randomized controlled trial assessing the efficacy of hydrocortisone administration on burn shock. Using whole genome microarrays, we first compared burn patients from the placebo group (n=15) to healthy volunteers (n=13) to describe the transcriptional modulation induced by burn shock over the first week. Then we compared burn patients randomized for either hydrocortisone administration (n=15) or placebo (n=15) to assess hydrocortisone-induced modulation. Measurements and Main Results: Study groups were similar in terms of severity and major outcomes, but shock duration (significantly reduced in the hydrocortisone group). Many genes (n=2250) were differentially expressed between burn patients and healthy volunteers, with 85% of them exhibiting a profound and persistent modulation over seven days. Interestingly, we showed that hydrocortisone enhanced the shock-associated repression of adaptive, but also innate immunity. Conclusions: We found that the initial host response to burn shock encompasses a wide and persistent modulation of gene expression, with profound modulation of pathways associated with metabolism and immunity. Importantly, hydrocortisone administration may worsen the immunosuppression associated with severe injury. These data should be taken into account in the risk ratio of hydrocortisone administration in patients with inflammatory shock. Overall design: Prospective randomized double blind study comparing hydrocortisone administration to placebo (NaCl 0.9%). Whole blood samples were collected at inclusion (S1, before treatment administration), one day after (S2, one day after treatment administration), and at a median of 120h (S3, 120h after treatment administration) and 168h (S4, 168h after treatment administration). 13 healthy volunteers (HV) were sampled to provide control for the microarray experiments.

INSTRUMENT(S): [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array

SUBMITTER: Julien Textoris  

PROVIDER: GSE77791 | GEO | 2017-07-02

SECONDARY ACCESSION(S): PRJNA311562

REPOSITORIES: GEO

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Publications

Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial.

Plassais Jonathan J   Venet Fabienne F   Cazalis Marie-Angélique MA   Le Quang Diane D   Pachot Alexandre A   Monneret Guillaume G   Tissot Sylvie S   Textoris Julien J  

Critical care (London, England) 20170616 1


Despite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm to the immune system. Few studies have assessed the impact of hydrocortisone on the transcriptional response in shock, and we are lacking data on burn shock. Our objective was to assess the hydrocortisone-induced transcriptional modulation in severe burn shock, particularly modulation of the immune response.We collected whole blood samples during a randomized controlled trial ass  ...[more]

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