title: Insights into the Role of Chemokines, Damage-Associated Molecular Patterns, and Lymphocyte-Derived Mediators from Computational Models of Trauma-Induced Inflammation.
abstract: CONCLUSIONS
  Traumatic injury elicits a complex, dynamic, multidimensional inflammatory response that is intertwined with complications such as multiple organ dysfunction and nosocomial infection. The complex interplay between inflammation and physiology in critical illness remains a challenge for translational research, including the extrapolation to human disease from animal models.
  
  
  BACKGROUND
  Over the past decade, we and others have attempted to decipher the biocomplexity of inflammation in these settings of acute illness, using computational models to improve clinical translation. In silico modeling has been suggested as a computationally based framework for integrating data derived from basic biology experiments as well as preclinical and clinical studies.
  
  
  RESULTS
  Extensive studies in cells, mice, and human blunt trauma patients have led us to suggest (i) that while an adequate level of inflammation is required for healing post-trauma, inflammation can be harmful when it becomes self-sustaining via a damage-associated molecular pattern/Toll-like receptor-driven feed-forward circuit; (ii) that chemokines play a central regulatory role in driving either self-resolving or self-maintaining inflammation that drives the early activation of both classical innate and more recently recognized lymphoid pathways; and (iii) the presence of multiple thresholds and feedback loops, which could significantly affect the propagation of inflammation across multiple body compartments.
  
  
  CONCLUSIONS
  These insights from data-driven models into the primary drivers and interconnected networks of inflammation have been used to generate mechanistic computational models. Together, these models may be used to gain basic insights as well as serving to help define novel biomarkers and therapeutic targets.
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Rami A
authors.initials: RA
authors.lastname: Namas
authors.affiliation: 3 Department of Sports Medicine and Nutrition, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Qi
authors.initials: Q
authors.lastname: Mi
authors.affiliation: 4 Department of Internal Medicine, Division of Rheumatology, University of Michigan , Ann Arbor, Michigan.
authors.forename: Rajaie
authors.initials: R
authors.lastname: Namas
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Khalid
authors.initials: K
authors.lastname: Almahmoud
authors.affiliation: 5 Department of Critical Care Medicine, University of Pittsburgh , Pennsylvania.
authors.forename: Akram M
authors.initials: AM
authors.lastname: Zaaqoq
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Othman
authors.initials: O
authors.lastname: Abdul-Malak
authors.affiliation: 6 Department of Computational and Systems Biology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Nabil
authors.initials: N
authors.lastname: Azhar
authors.affiliation: 7 Department of Mathematics, University of Tennessee , Knoxville, Tennessee.
authors.forename: Judy
authors.initials: J
authors.lastname: Day
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Andrew
authors.initials: A
authors.lastname: Abboud
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Ruben
authors.initials: R
authors.lastname: Zamora
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.affiliation: 1 Department of Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.|2 Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.|6 Department of Computational and Systems Biology, University of Pittsburgh , Pittsburgh, Pennsylvania.
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
mesh_terms: D000818:Animals; D018925:Chemokines / Q000378:metabolism*; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D057170:Translational Research, Biomedical; D014947:Wounds and Injuries / Q000276:immunology*
chemical_list: D018925:Chemokines