title: Protection from experimental ventilator-induced acute lung injury by IL-1 receptor blockade.
abstract: BACKGROUND
  Clinical studies have shown that injurious mechanical ventilation is associated with increased airspace and plasma levels of interleukin-1beta (IL-1beta); however, the potential therapeutic value of IL-1 inhibition in acute lung injury has not been thoroughly investigated. A study was undertaken to determine if IL-1 signalling is a necessary early event in the pathogenesis of experimental ventilator-induced lung injury.
  
  
  METHODS
  Mice deficient in IL-1 receptor type 1 (IL1R1) and rats treated with IL-1 receptor antagonist (IL-1Ra) were mechanically ventilated with high tidal volume (30 ml/kg) and the effect of IL-1 signalling blockade on the severity of lung injury was determined.
  
  
  RESULTS
  Permeability, as measured by radiolabelled albumin flux, was significantly lower in IL1R1 null mice than in wild-type mice during injurious ventilation (p<0.05). IL-1Ra significantly decreased protein permeability and pulmonary oedema in rats during injurious ventilation and also decreased airspace and plasma levels of the chemokine CXCL1 and airspace neutrophils. IL-1Ra decreased expression of NOS2 and ICAM-1 mRNA in whole lung. Bronchoalveolar lavage fluid levels of RTI40, a marker of type I cell injury, were 2.5 times lower following IL-1Ra treatment (p<0.05). In isolated type II pneumocytes, IL-1beta reduced electrical resistance and increased transepithelial permeability.
  
  
  CONCLUSIONS
  IL-1 contributes to alveolar barrier dysfunction in VILI by promoting lung neutrophil recruitment and by increasing epithelial injury and permeability. Because preserved alveolar barrier function is associated with better outcomes in patients with acute lung injury, these data support further testing of IL-1Ra for the treatment of acute lung injury.
authors: Cardiovascular Research Institute, University of California, San Francisco VA Medical Center, 4150 Clement St, Box 111D, San Francisco, CA 94121, USA. james.frank@ucsf.edu
authors: J A
authors: JA
authors: Frank
authors: J-F
authors: JF
authors: Pittet
authors: C
authors: C
authors: Wray
authors: M A
authors: MA
authors: Matthay
mesh_terms: D000818:Animals; D002450:Cell Communication; D015601:Injury Severity Score; D051379:Mice; D008822:Mice, Transgenic; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012121:Respiration, Artificial / Q000009:adverse effects*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D013990:Tidal Volume
chemical_list: D017472:Receptors, Interleukin-1