Elevated endogenous surfactant reduces inflammation in an acute lung injury model.
Acute lung injury (ALI) is associated with severe pulmonary inflammation and alterations to surfactant, and often results in overwhelming systemic inflammation, leading to multiple organ failure. The objective of this study was to determine the effect of increased endogenous surfactant pools on pulmonary and systemic inflammation in a model of lipopolysaccharide (LPS)-induced ALI. Mice received an instillation of liposome-encapsulated (i) dichloromethylene diphosphonic acid (DMDP) to increase surfactant pools via depletion of alveolar macrophages, or (ii) phosphate-buffered saline (PBS). Seven days after instillation, mice received an intranasal administration of LPS or saline. Following a 4-hour recovery period, mice were sacrificed and their lungs were isolated, mechanically ventilated, and perfused with 8 mL of recirculated perfusate through the pulmonary circulation for 2 hours. Perfusate and lavage fluid were collected for analysis of inflammatory mediators. Lavage analysis revealed a 5-fold increase in surfactant pools in DMDP-treated mice compared to PBS-treated controls. Lavage and perfusate analyses showed significant decreases in the concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, and IL-1beta cytokines in DMDP-LPS mice compared to PBS-LPS controls. Elevated endogenous surfactant pools are protective against both LPS- and mechanical ventilation-induced inflammation, in addition to inflammation associated with the combination of these two insults.
Department of Physiology and Pharmacology, Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada.
Melissa G
MG
Walker
Jenna M
JM
Tessolini
Lynda
L
McCaig
Li-Juan
LJ
Yao
James F
JF
Lewis
Ruud A W
RA
Veldhuizen
D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D004002:Clodronic Acid / Q000008:administration & dosage; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008081:Liposomes; D016676:Macrophages, Alveolar / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011663:Pulmonary Surfactants / Q000378:metabolism*
D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008081:Liposomes; D011663:Pulmonary Surfactants; D004002:Clodronic Acid