In vivo effect of surfactant on inflammatory cytokines during endotoxin-induced lung injury in rodents

J Immunotoxicol. Oct-Dec 2011;8(4):274-83. doi: 10.3109/1547691X.2011.591294. Epub 2011 Jul 18.

Abstract

Lipopolysaccharide (LPS) is a known inducer of acute respiratory distress syndrome (ARDS) in humans and animals. In this study, ARDS was developed in rats by intratracheal instillation of LPS and the effect of two types of surfactant (natural vs. synthetic) was examined to determine their potential corrective roles in general, as well as to compare the two surfactants against one another in particular, in endotoxin-induced lung injury. Sprague-Dawley male rats were divided into four groups, i.e., rats given: buffer controls; 055:B5 E. coli LPS only; LPS and then porcine surfactant (P-SF); or, LPS and then synthetic surfactant (S-SF). In vivo administration of LPS led to an increase in expression of the cytokines tumor necrosis factor-α, interleukin (IL)-1β, IL-2, IL-4, interferon-γ, monocyte chemotactic protein-1, and macrophage inflammatory protein-1β in the lungs of rats. These effects were confirmed by immunofluorescence in lung tissue sections and/or by protein (Western immunoblot) and mRNA expression (reverse transcription polymerase chain reaction) analyses of tissue samples. Apart from IL-4, concentrations of each of these cytokines in bronchoalveolar lavage fluid recovered from the animals were significantly increased in the LPS-treated hosts. Instillation of either surfactant (70 h after the LPS) into the airways diminished the expression of each of the inducible-cytokines, with the porcine (natural) form seeming having the greater inhibitory effect. These data suggest that surfactant can play an important role in the treatment of endotoxin-induced lung injury and might possess robust anti-inflammatory effects. Further, it seems that both the natural and synthetic surfactants prevent inflammatory outcomes in the lungs by controlling cytokine(s) production by various inflammatory cells. Last, the studies here clearly indicated that in this aspect, natural surfactant appears to be more beneficial compared to synthetic surfactant.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / chemically induced*
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / metabolism
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism
  • Cytokines / analysis
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Gene Expression / drug effects
  • Interferon-gamma / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism
  • Lipopolysaccharides / toxicity*
  • Lung / drug effects*
  • Lung / immunology
  • Male
  • Microscopy, Fluorescence
  • Pulmonary Surfactants / pharmacology*
  • Rabbits
  • Rats
  • Rats, Sprague-Dawley
  • Swine
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Chemokine CCL2
  • Cytokines
  • Interleukins
  • Lipopolysaccharides
  • Pulmonary Surfactants
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma