title: Computational Analysis Supports an Early, Type 17 Cell-Associated Divergence of Blunt Trauma Survival and Mortality.
abstract: OBJECTIVE
  Blunt trauma patients may present with similar demographics and injury severity yet differ with regard to survival. We hypothesized that this divergence was due to different trajectories of systemic inflammation and utilized computational analyses to define these differences.
  
  
  METHODS
  Retrospective clinical study and experimental study in mice.
  
  
  METHODS
  Level 1 trauma center and experimental laboratory.
  
  
  METHODS
  From a cohort of 493 victims of blunt trauma, we conducted a pairwise, retrospective, case-control study of patients who survived over 24 hours but ultimately died (nonsurvivors; n = 19) and patients who, after ICU admission, went on to be discharged(survivors; n = 19).
  
  
  METHODS
  None in patients. Neutralizing anti-interleukin-17A antibody in mice.
  
  
  RESULTS
  Data on systemic inflammatory mediators assessed within the first 24 hours and over 7 days were analyzed with computational modeling to infer dynamic networks of inflammation. Network density among inflammatory mediators in nonsurvivors increased in parallel with organ dysfunction scores over 7 days, suggesting the presence of early, self-sustaining, pathologic inflammation involving high-mobility group protein B1, interleukin-23, and the Th17 pathway. Survivors demonstrated a pattern commensurate with a self-resolving, predominantly lymphoid response, including higher levels of the reparative cytokine interleukin-22. Mice subjected to trauma/hemorrhage exhibited reduced organ damage when treated with anti-interleukin-17A.
  
  
  CONCLUSIONS
  Variable type 17 immune responses are hallmarks of organ damage, survival, and mortality after blunt trauma and suggest a lymphoid cell-based switch from self-resolving to self-sustaining inflammation.
authors: 1Department of Surgery, University of Pittsburgh, Pittsburgh, PA. 2Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA. 3Department of Computational & Systems Biology, University of Pittsburgh, Pittsburgh, PA. 4Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA. 5Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI. 6Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, Pittsburgh, PA.
authors: Andrew
authors: A
authors: Abboud
authors: Rami A
authors: RA
authors: Namas
authors: Mostafa
authors: M
authors: Ramadan
authors: Qi
authors: Q
authors: Mi
authors: Khalid
authors: K
authors: Almahmoud
authors: Othman
authors: O
authors: Abdul-Malak
authors: Nabil
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authors: Azhar
authors: Akram
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authors: Zaaqoq
authors: Rajaie
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authors: Namas
authors: Derek A
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authors: Barclay
authors: Jinling
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authors: Yin
authors: Jason
authors: J
authors: Sperry
authors: Andrew
authors: A
authors: Peitzman
authors: Ruben
authors: R
authors: Zamora
authors: Richard L
authors: RL
authors: Simmons
authors: Timothy R
authors: TR
authors: Billiar
authors: Yoram
authors: Y
authors: Vodovotz
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016022:Case-Control Studies; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000401:mortality; D020381:Interleukin-17 / Q000037:antagonists & inhibitors / Q000097:blood; D053759:Interleukin-23 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D063305:Organ Dysfunction Scores; D012189:Retrospective Studies; D058504:Th17 Cells / Q000378:metabolism*; D014949:Wounds, Nonpenetrating / Q000401:mortality*; D000097043:Interleukin-22
chemical_list: D000906:Antibodies; D024243:HMGB1 Protein; D020381:Interleukin-17; D053759:Interleukin-23; D007378:Interleukins; D000097043:Interleukin-22