Survival after multiple traumas is associated with improved outcomes from gram-negative sepsis: Clinical and experimental evidence

Objectives: We investigated the susceptibility to Gram-negative sepsis after multiple traumas (MT). Methods: From a prospective cohort of 5076 Greek patients with sepsis, 16 with Gram-negative bacteremia after MT were compared with 204 patients well-matched for severity, comorbidities and appropriateness of antimicrobials; circulatingmononuclear cells were isolated and stimulated for the release of interleukin (IL)-10. Male C57Bl6J mice were subject to MT (right pneumothorax and right femur fracture) followed after 72 h by the intravenous challenge with Pseudomonas aeruginosa. Survival was recorded and splenocytes were isolated for cytokine stimulation. Results: 28-daymortality afterMTwas 18.8% compared to 48.0% of comparators (48.0%) (odds ratio 0.25, p: 0.035). This was confirmed after logistic regression analysis taking into consideration comorbidities and age. Stimulation of IL-10 was enhanced from MT patients. Survival of mice challenged by P. aeruginosa 72 h after MTwas prolonged compared tomice challenged by P. aeruginosa without prior MT. Cytokine production was decreased 24 h after MT and restored 96 h thereafter. Production of IL-10 was particularly pronounced fromsplenocytes ofmice challenged by P. aeruginosa after MT. Conclusions: Survival after MT is accompanied by favorable immune responses allowing survival benefit from Gram-negative sepsis. This is associated with increased IL-10 release. (C) 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.