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

- Prior multiple trauma (MT) provides survival benefit from Gram-negative sepsis.
- This is associated with increased IL-10 production by circulating monocytes.
- Prior MT provides survival benefit from experimental P. aeruginosa infection.
- Increased IL-10 production and lower bacterial outgrowth are potential mechanisms.

SummaryObjectivesWe investigated the susceptibility to Gram-negative sepsis after multiple traumas (MT).MethodsFrom 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; circulating mononuclear 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.Results28-day mortality after MT was 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 MT was prolonged compared to mice 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 from splenocytes of mice challenged by P. aeruginosa after MT.ConclusionsSurvival after MT is accompanied by favorable immune responses allowing survival benefit from Gram-negative sepsis. This is associated with increased IL-10 release.