title: Inducible protein-10, a potential driver of neurally controlled interleukin-10 and morbidity in human blunt trauma.
abstract: OBJECTIVE
  Blunt trauma and traumatic spinal cord injury induce systemic inflammation that contributes to morbidity. Dysregulated neural control of systemic inflammation postinjury is likely exaggerated in patients with traumatic spinal cord injury. We used in silico methods to discern dynamic inflammatory networks that could distinguish systemic inflammation in traumatic spinal cord injury from blunt trauma.
  
  
  METHODS
  Retrospective study.
  
  
  METHODS
  Tertiary care institution.
  
  
  METHODS
  Twenty-one severely injured thoracocervical traumatic spinal cord injury patients and matched 21 severely injured blunt trauma patients without spinal cord injury.
  
  
  METHODS
  None.
  
  
  RESULTS
  Serial blood samples were obtained from days 1 to 14 postinjury. Twenty-four plasma inflammatory mediators were quantified. Statistical significance between the two groups was determined by two-way analysis of variance. Dynamic Bayesian network inference was used to suggest dynamic connectivity and central inflammatory mediators. Circulating interleukin-10 was significantly elevated in thoracocervical traumatic spinal cord injury group versus non-spinal cord injury group, whereas interleukin-1β, soluble interleukin-2 receptor-α, interleukin-4, interleukin-5, interleukin-7, interleukin-13, interleukin-17, macrophage inflammatory protein 1α and 1β, granulocyte-macrophage colony-stimulating factor, and interferon-γ were significantly reduced in traumatic spinal cord injury group versus non-spinal cord injury group. Dynamic Bayesian network suggested that post-spinal cord injury interleukin-10 is driven by inducible protein-10, whereas monocyte chemotactic protein-1 was central in non-spinal cord injury dynamic networks. In a separate validation cohorts of 356 patients without spinal cord injury and 85 traumatic spinal cord injury patients, individuals with plasma inducible protein-10 levels more than or equal to 730 pg/mL had significantly prolonged hospital and ICU stay and days on mechanical ventilator versus patients with plasma inducible protein-10 level less than 730 pg/mL.
  
  
  CONCLUSIONS
  This is the first study to compare the dynamic systemic inflammatory responses of traumatic spinal cord injury patients versus patients without spinal cord injury, suggesting a key role for inducible protein-10 in driving systemic interleukin-10 and morbidity and highlighting the potential utility of in silico tools to identify key inflammatory drivers.
authors.affiliation: 1Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA. 2Department of Surgery, University of Pittsburgh, Pittsburgh, PA. 3Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA. 4Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA. 5Department of Rehabilitation Science and Technology, University of Pittsburgh, Pittsburgh, PA. 6Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Akram M
authors.initials: AM
authors.lastname: Zaaqoq
authors.forename: Rami
authors.initials: R
authors.lastname: Namas
authors.forename: Khalid
authors.initials: K
authors.lastname: Almahmoud
authors.forename: Nabil
authors.initials: N
authors.lastname: Azhar
authors.forename: Qi
authors.initials: Q
authors.lastname: Mi
authors.forename: Ruben
authors.initials: R
authors.lastname: Zamora
authors.forename: David M
authors.initials: DM
authors.lastname: Brienza
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D054357:Chemokine CXCL10 / Q000097:blood* / Q000276:immunology; D018925:Chemokines / Q000097:blood; D015331:Cohort Studies; D003198:Computer Simulation; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood*; D015601:Injury Severity Score; D016753:Interleukin-10 / Q000097:blood*; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D009589:Nitrogen Oxides / Q000097:blood; D012189:Retrospective Studies; D013119:Spinal Cord Injuries / Q000097:blood*; D014949:Wounds, Nonpenetrating / Q000097:blood*
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D016207:Cytokines; D009589:Nitrogen Oxides; D016753:Interleukin-10