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

Critical Care

Diane Le Quang¹  Fabienne Venet¹  Guillaume Monneret¹  Julien Textoris²  Jonathan Plassais²  Alexandre Pachot²  Marie-Angélique Cazalis²  Sylvie Tissot³ 

[1] “Pathophysiology of injury induced immunosuppression (PI3)”, hôpital E. Herriot;EA7426, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, bioMérieux ;Hospices Civils de Lyon, Burn ICU, Anesthesia and Critical Care Medicine department, hôpital E. Herriot;

关键词: Shock;    Burns;    Hydrocortisone;    Transcriptome modulation;    Immunosuppression;    Host response;   

DOI  :  10.1186/s13054-017-1743-9

来源: DOAJ

【 摘 要 】

Abstract Background 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. Methods We 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. Results Study 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. Conclusions We 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 registration ClinicalTrials.gov, NCT00149123 . Registered on 6 September 2005.

【 授权许可】

Unknown