title: Cytokines and biotrauma in ventilator-induced lung injury: a critical review of the literature.
abstract: BACKGROUND
  Mechanical ventilation is known to induce and aggravate lung injury. One of the underlying mechanisms is biotrauma, an inflammatory response in which cytokines play a crucial role.
  
  
  OBJECTIVE
  To review the literature on the role of cytokines in ventilator-induced lung injury (VILI) and multiple organ dysfunction syndrome (MODS).
  
  
  METHODS
  57 English written, peer-reviewed articles on cytokines in in-vitro settings (n=5), ex-vivo models (n=9) in-vitro models (n=19) and clinical trials (n=24).
  
  
  RESULTS
  Mechanical ventilation (MV) can induce cytokine upregulation in both healthy and injured lungs. The underlying mechanisms include alveolar cellular responses to stretch with subsequent decompartimentalisation due to concomitant cellular barrier damage. The cytokines involved are interleukin (IL)-8 and CXC chemokines, and probably IL-6, IL-1beta and tumour necrosis factor (TNF)-alpha. Cytokines are important for signalling between inflammatory cells and recruiting leucocytes to the lung. There is strong circumstantial evidence that the release of cytokines into the systemic circulation contributes to the pathogenesis of MODS. Multiple studies demonstrate the relation between elevated proinflammatory cytokine concentrations and mortality.
  
  
  CONCLUSIONS
  Cytokines are likely to play a role in the various interrelated processes that lead to VILI and other MV-related complications, such as MODS and possibly ventilatorassociated pneumonia. Cytokines are good surrogate endpoints in exploring the pathogenesis and pathophysiology of VILI in both experimental and clinical studies.
authors.affiliation: Department of Paediatric Intensive Care, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. F.Halbertsma@mmc.nl
authors.forename: F J J
authors.initials: FJ
authors.lastname: Halbertsma
authors.forename: M
authors.initials: M
authors.lastname: Vaneker
authors.forename: G J
authors.initials: GJ
authors.lastname: Scheffer
authors.forename: J G
authors.initials: JG
authors.lastname: van der Hoeven
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D008168:Lung / Q000276:immunology*; D055370:Lung Injury; D009102:Multiple Organ Failure / Q000209:etiology; D018746:Systemic Inflammatory Response Syndrome / Q000209:etiology; D012122:Ventilators, Mechanical / Q000009:adverse effects*
chemical_list: D016207:Cytokines