title: Evolution of the inflammatory and fibroproliferative responses during resolution and repair after ventilator-induced lung injury in the rat.
abstract: BACKGROUND
  The time course and mechanisms of resolution and repair, and the potential for fibrosis following ventilation-induced lung injury (VILI), are unclear. We sought to examine the pattern of inflammation, injury, repair, and fibrosis following VILI.
  
  
  METHODS
  Sixty anesthetized rats were subject to high-stretch; low-stretch, or sham ventilation, and randomly allocated to undergo periods of recovery of 6, 24, 48, and 96 h, and 7 and 14 days. Animals were then reanesthetized, and the extent of lung injury, inflammation, and repair determined.
  
  
  RESULTS
  No injury was seen following low-stretch or sham ventilation. VILI caused severe lung injury, maximal at 24 h, but largely resolved by 96 h. Arterial oxygen tension decreased from a mean (SD) of 144.8 (4.1) mmHg to 96.2 (10.3) mmHg 6 h after VILI, before gradually recovering to 131.2 (14.3) mmHg at 96 h. VILI induced an early neutrophilic alveolitis and a later lymphocytic alveolitis, followed by a monocyte/macrophage infiltration. Alveolar tumor necrosis factor-α, interleukin-1β, and transforming growth factor-β1 concentrations peaked at 6 h and returned to baseline within 24 h, while interleukin-10 remained increased for 48 h. VILI generated a marked but transient fibroproliferative response, which restored normal lung architecture. There was no evidence of fibrosis at 7 and 14 days.
  
  
  CONCLUSIONS
  High-stretch ventilation caused severe lung injury, activating a transient inflammatory and fibroproliferative repair response, which restored normal lung architecture without evidence of fibrosis.
authors.affiliation: Department of Anaesthesia, Clinical Sciences Institute, and Lung Biology Group, National Centre for Biomedical Engineering Sciences, National University of Ireland, Galway, Ireland.
authors.forename: Gerard F
authors.initials: GF
authors.lastname: Curley
authors.forename: Maya
authors.initials: M
authors.lastname: Contreras
authors.forename: Brendan
authors.initials: B
authors.lastname: Higgins
authors.forename: Cecilia
authors.initials: C
authors.lastname: O'Kane
authors.forename: Daniel F
authors.initials: DF
authors.lastname: McAuley
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Toole
authors.forename: John G
authors.initials: JG
authors.lastname: Laffey
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D003094:Collagen / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D005355:Fibrosis; D007249:Inflammation / Q000209:etiology*; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D055397:Ventilator-Induced Lung Injury / Q000473:pathology* / Q000503:physiopathology
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D003094:Collagen; D020782:Matrix Metalloproteinases