Survival after multiple traumas is associated with improved outcomes from gram-negative sepsis: Clinical and experimental evidence.
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.
4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
Eleftherios
E
Mandragos
4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
Aikaterini
A
Pistiki
2nd Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
Iraklis
I
Tsangaris
1st Department of Critical Care Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
Christina
C
Routsi
Intensive Care Unit, "Korgialeneion-Benakeion" General Hospital, Athens, Greece.
Michael
M
Paraschos
4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece.
Dionyssia-Irene
DI
Droggiti
1st Department of Orthopaedics, National and Kapodistrian University of Athens, Medical School, Greece.
Olga
O
Savvidou
1st Department of Orthopaedics, National and Kapodistrian University of Athens, Medical School, Greece.
Dimitrios
D
Mastrokalos
1st Department of Orthopaedics, National and Kapodistrian University of Athens, Medical School, Greece.
Panayiotis J
PJ
Papagelopoulos
Department of Internal Medicine, Radboud University Nijmegen, The Netherlands.
Mihai G
MG
Netea
4th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece. Electronic address: egiamarel@med.uoa.gr.
Evangelos J
EJ
Giamarellos-Bourboulis
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015331:Cohort Studies; D015897:Comorbidity; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004198:Disease Susceptibility; D005260:Female; D006090:Gram-Negative Bacteria / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009104:Multiple Trauma / Q000276:immunology* / Q000382:microbiology; D011446:Prospective Studies; D011552:Pseudomonas Infections / Q000276:immunology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000302:isolation & purification; D012044:Regression Analysis; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D013154:Spleen / Q000166:cytology; D016019:Survival Analysis
D016207:Cytokines; C508609:IL10 protein, human; D016753:Interleukin-10
Cytokines; Interleukin-10; Multiple trauma; Sepsis; Survival