title: The immune response to surgery and trauma:  Implications for treatment.
abstract: BACKGROUND
  Infection after surgery and trauma is a major cause of increased morbidity, mortality, and cost. Alterations of the hosts immune system following these insults is believed to be responsible for the increased risk of infection. The hosts' immune response to tissue injury is widely believed to follow a bimodal response, with the systemic inflammatory response syndrome (SIRS) followed by the compensated anti-inflammatory response syndrome (CARS). Recent data, however, suggests that his paradigm may not be correct.
  
  
  METHODS
  We reviewed the literature to describe the immunological changes following surgery and trauma and possible therapeutic interventions to limit this process.
  
  
  RESULTS
  Physical injury related to trauma and surgery increase the expression of T-helper 2 (Th2) lymphocytes which cause impaired cell mediated immunity (CMI). Activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathoadrenal system (SAS) with the release of cortisol and catecholamines appear to be responsible for altering the Th1/Th2 balance. Decreased expression and signalling of interleukin-12 (IL-12) and increased expression of T regulatory cells (Tregs) appear to play a central role in mediating this immune depression. Furthermore, Th2 cytokines increase the expression of arginase-1 (ARG1) in myeloid-derived suppressor cells (MDSC's) causing an arginine deficient state, which further impairs lymphocyte function. Immunomodulating diets (IMDs) containing supplemental arginine and omega-3 fatty acids have been demonstrated to restore the Th1/Th2 balance after surgical trauma and to reduce the risk of infectious complications. β-adrenergic receptor blockage reverses the Th-1 to Th2 shift and preliminary data suggests that such therapy may be beneficial.
  
  
  CONCLUSIONS
  Tissue injury following surgery and trauma results in depressed CMI leading to an increased risk of infections. The peri-operative use of IMDs appear to reverse this immunosuppression and decrease the risk of postoperative complications. While β-adrenoreceptor blockage may be beneficial in these patients, particularly when combined with a IMD, additional research is required.
authors.affiliation: Divisions of General Internal Medicine, Eastern Virginia Medical School, Norfolk, Virginia, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Marik
authors.forename: Mark
authors.initials: M
authors.lastname: Flemmer
mesh_terms: D058671:Adrenergic beta-1 Receptor Antagonists / Q000627:therapeutic use*; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D007111:Immunity, Cellular; D013530:Surgical Wound Infection / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D018746:Systemic Inflammatory Response Syndrome / Q000188:drug therapy / Q000209:etiology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014947:Wounds and Injuries / Q000150:complications / Q000276:immunology* / Q000378:metabolism
chemical_list: D058671:Adrenergic beta-1 Receptor Antagonists; D016207:Cytokines