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

• Published in: The Journal of infection Vol. 74; no. 2; pp. 163 - 171
• Main Authors: Mandragos, Eleftherios, Pistiki, Aikaterini, Tsangaris, Iraklis, Routsi, Christina, Paraschos, Michael, Droggiti, Dionyssia-Irene, Savvidou, Olga, Mastrokalos, Dimitrios, Papagelopoulos, Panayiotis J., Netea, Mihai G., Giamarellos-Bourboulis, Evangelos J.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2017
• Subjects: Aged; Aged, 80 and over; Animals; Cohort Studies; Comorbidity; Cytokines; Cytokines - biosynthesis; Cytokines - immunology; Disease Susceptibility; Female; Gram-Negative Bacteria - isolation & purification; Gram-Negative Bacterial Infections - drug therapy; Gram-Negative Bacterial Infections - immunology; Gram-Negative Bacterial Infections - microbiology; Humans; Infectious Disease; Interleukin-10; Interleukin-10 - immunology; Interleukin-10 - secretion; Leukocytes, Mononuclear - drug effects; Male; Mice; Mice, Inbred C57BL; Middle Aged; Multiple trauma; Multiple Trauma - immunology; Multiple Trauma - microbiology; Prospective Studies; Pseudomonas aeruginosa - immunology; Pseudomonas aeruginosa - isolation & purification; Pseudomonas Infections - immunology; Pseudomonas Infections - microbiology; Regression Analysis; Sepsis; Sepsis - drug therapy; Sepsis - immunology; Sepsis - microbiology; Spleen - cytology; Survival; Survival Analysis; Sepsis; Multiple trauma; Cytokines; Interleukin-10; Survival
• ISSN: 0163-4453; 1532-2742
• DOI: 10.1016/j.jinf.2016.10.007

We investigated the susceptibility to Gram-negative sepsis after multiple traumas (MT). 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. 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. Survival after MT is accompanied by favorable immune responses allowing survival benefit from Gram-negative sepsis. This is associated with increased IL-10 release. •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.