title: The effects of exogenous surfactant administration on ventilation-induced inflammation in mouse models of lung injury.
abstract: BACKGROUND
  Mechanical ventilation (MV) is an essential supportive therapy for acute lung injury (ALI); however it can also contribute to systemic inflammation. Since pulmonary surfactant has anti-inflammatory properties, the aim of the study was to investigate the effect of exogenous surfactant administration on ventilation-induced systemic inflammation.
  
  
  METHODS
  Mice were randomized to receive an intra-tracheal instillation of a natural exogenous surfactant preparation (bLES, 50 mg/kg) or no treatment as a control. MV was then performed using the isolated and perfused mouse lung (IPML) set up. This model allowed for lung perfusion during MV. In experiment 1, mice were exposed to mechanical ventilation only (tidal volume =20 mL/kg, 2 hours). In experiment 2, hydrochloric acid or air was instilled intra-tracheally four hours before applying exogenous surfactant and ventilation (tidal volume =5 mL/kg, 2 hours).
  
  
  RESULTS
  For both experiments, exogenous surfactant administration led to increased total and functional surfactant in the treated groups compared to the controls. Exogenous surfactant administration in mice exposed to MV only did not affect peak inspiratory pressure (PIP), lung IL-6 levels and the development of perfusate inflammation compared to non-treated controls. Acid injured mice exposed to conventional MV showed elevated PIP, lung IL-6 and protein levels and greater perfusate inflammation compared to air instilled controls. Instillation of exogenous surfactant did not influence the development of lung injury. Moreover, exogenous surfactant was not effective in reducing the concentration of inflammatory cytokines in the perfusate.
  
  
  CONCLUSIONS
  The data indicates that exogenous surfactant did not mitigate ventilation-induced systemic inflammation in our models. Future studies will focus on altering surfactant composition to improve its immuno-modulating activity.
authors.affiliation: Department of Physiology & Pharmacology, Western University, London, Ontario, Canada. vpuntori@uwo.ca.
authors.forename: Valeria
authors.initials: V
authors.lastname: Puntorieri
authors.forename: Josh Qua
authors.initials: JQ
authors.lastname: Hiansen
authors.forename: Lynda A
authors.initials: LA
authors.lastname: McCaig
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Yao
authors.forename: Ruud A W
authors.initials: RA
authors.lastname: Veldhuizen
authors.forename: James F
authors.initials: JF
authors.lastname: Lewis
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000628:therapy*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000032:analysis / Q000378:metabolism; D006851:Hydrochloric Acid; D007249:Inflammation / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D010539:Permeability / Q000187:drug effects; D011175:Positive-Pressure Respiration / Q000009:adverse effects; D011663:Pulmonary Surfactants / Q000627:therapeutic use*; D014109:Total Lung Capacity / Q000187:drug effects
chemical_list: D016207:Cytokines; D015777:Eicosanoids; D015850:Interleukin-6; D011663:Pulmonary Surfactants; D006851:Hydrochloric Acid