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.
Highlights
Despite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm to the immune system
Hydrocortisone modulation of vascular tone at the transcriptional level As hydrocortisone has been shown to reduce the duration of septic shock [10, 31] and severe burn shock [20], we explored selected mechanisms involved in vascular tone control: the modulation of adrenergic and nitric oxide (NO) pathways at the transcriptional level
The initial response to burn shock encompasses wide and persistent genomic modulation, with a profound alteration of pathways associated with metabolism and immunity
Summary
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, modulation of the immune response. Transplantation, inflammatory, and auto-immune diseases have benefitted from the immunomodulatory properties of glucocorticoids for decades. Glucocorticoids modulate both innate and adaptive immune. Considering the aforementioned effects, it seems logical that glucocorticoids may avoid the deadly effect of the massive inflammatory response initially seen in sepsis. The precise molecular mechanisms are still largely unknown, nitric oxide (NO) synthesis seems to play a determinant role in modulating the vascular tone over the initial course after injury [16, 17]
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