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

Abstract

BackgroundDespite 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.MethodsWe collected whole blood samples during a randomized controlled trial assessing the efficacy of hydrocortisone administration in burn shock. Using whole genome microarrays, we first compared burn patients (n = 32) from the placebo group to healthy volunteers to describe the transcriptional modulation induced by burn shock over the first week. Then we compared burn patients randomized for either hydrocortisone administration or placebo, to assess hydrocortisone-induced modulation.ResultsStudy groups were similar in terms of severity and major outcomes, but shock duration was significantly reduced in the hydrocortisone group. Many genes (n = 1687) 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.ConclusionsWe found that the initial host response to burn shock encompasses 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.Trial registrationClinicalTrials.gov, NCT00149123. Registered on 6 September 2005.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-017-1743-9) contains supplementary material, which is available to authorized users.

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

“…30 severe burn patients admitted at Hospices Civils de Lyon, France (HCL) were included in a placebo-controlled, randomized, double-blind study assessing the efficacy of hydrocortisone administration on burn shock duration. Inclusion / exclusion criteria, clinical description and ethical considerations of the cohort have been previously published elsewhere (Venet et al 2015; Plassais et al 2017). Thirteen healthy volunteers were also recruited within Hospices Civils de Lyon to serve as controls for the transcriptional study.…”

“…After severe injuries like septic shock, burn or trauma, leading to an important inflammatory response, we and others have shown that the blood transcriptome is highly modulated, with early and profound changes in adaptive and innate immune responses (Plassais et al 2017; Xiao et al 2011). Moreover in these contexts, viral reactivation is often observed, especially for Herpes Viruses (Ong et al 2017; Textoris and Mallet 2017).…”

Individualizing Optimal Fluid Resuscitation in Patients with Major Burns: Emerging Role for Hydrocortisone, Proteinuria and Brain Natriuretic Peptide

“…These inflammatory response parameters are reported not only to depend on burn size but also to differ between individuals [12-16]. These differences may be explained in part by differences in each individual genetic make-up [17,18]. Burn trauma also induces coagulopathy and combining a patient's early coagulation and inflammatory status in addition to standard clinical indices improves prognostic models [19].…”

“…Recently however, several studies with low-dose hydrocortisone started immediately after admission were reported to improve outcome in patients with major burns [21][22][23]31,32]. Hydrocortisone differentially regulates cytokine responses and modulates transcriptional processes [18,33]. This provides a physiological understanding of the mechanism of action of hydrocortisone on cytokine responses and thus on capillary leakage.…”

Endogenous Retroviruses Transcriptional Modulation After Severe Infection, Trauma and Burn

“…After severe injuries like septic shock, burn or trauma, leading to an important inflammatory response, we and others have shown that the blood transcriptome is highly modulated, with early and profound changes in adaptive and innate immune responses (16, 17). Moreover, in these contexts, viral reactivation is often observed, especially for Herpes Viruses (18, 19).…”