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Published on: June 15, 2019
Survival after multiple traumas is associated with improved outcomes from gram-negative sepsis: Clinical and
Eleftherios Mandragos1, Aikaterini Pistiki1, Iraklis Tsangaris2
14th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
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; 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.
Results:
28-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.
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.
Insights
Multiple trauma (MT) survivors show improved outcomes from Gram-negative sepsis due to enhanced immune responses. This survival benefit is linked to increased interleukin-10 (IL-10) release, observed in both human patients and animal models.
Area of Science:
- Immunology
- Critical Care Medicine
- Trauma Surgery
Background:
- Gram-negative sepsis is a significant cause of mortality in critically ill patients.
- The immune response following multiple trauma (MT) can influence sepsis outcomes.
- Interleukin-10 (IL-10) is a key immunosuppressive cytokine with a complex role in infection.
Purpose of the Study:
- To investigate the association between multiple trauma (MT) and susceptibility to Gram-negative sepsis.
- To explore the role of interleukin-10 (IL-10) in the immune response to Gram-negative sepsis after MT.
- To evaluate survival rates and immune cell responses in patients and animal models with Gram-negative sepsis post-MT.
Main Methods:
- A prospective cohort study compared 16 Gram-negative bacteremia patients with MT to 204 matched controls.
- Mice underwent MT followed by Pseudomonas aeruginosa challenge; survival and splenocyte cytokine production were assessed.
- Circulating mononuclear cells from patients were stimulated to measure IL-10 release.
Main Results:
- 28-day mortality was significantly lower in MT patients (18.8%) compared to controls (48.0%) (OR 0.25, p=0.035).
- IL-10 stimulation was enhanced in MT patients.
- Mice with prior MT exhibited prolonged survival following P. aeruginosa challenge, with increased IL-10 production from splenocytes.
Conclusions:
- Survival after multiple trauma is associated with a beneficial immune response that enhances survival from Gram-negative sepsis.
- Increased interleukin-10 (IL-10) release appears to be a key mechanism mediating this survival benefit.
- These findings suggest a potential immunomodulatory role for IL-10 in sepsis following trauma.
