Published: 21. Jul 2010

Ni YF, Tian F, Lu ZF, Yang GD, Fu HY, Wang J, Yan XL, Zhao YC, Wang YJ, Jiang T

Protective Effect of Nicotine on Lipopolysaccharide-Induced Acute Lung Injury in Mice.
(Respiration)


BACKGROUND: Recently, nicotine administration has been shown to be a potent inhibitor of a variety of innate immune responses, including endotoxin-induced sepsis.

OBJECTIVE: It was the aim of this study to evaluate the effect of nicotine on attenuating lung injury and improving the survival in mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI). Methods: ALI was induced in mice by intratracheal instillation of LPS (3 mg/ml). The mice received intratracheal instillation of nicotine (50, 250 and 500 mug/kg) before or after LPS administration. Pulmonary histological changes were evaluated by hematoxylin-eosin stain, and lung wet/dry weight ratios were observed. Concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and high mobility group box (HMGB)-1, as well as myeloperoxidase (MPO) activity were measured by enzyme-linked immunosorbent assay. The mortality rate was recorded and analyzed by the Kaplan-Meier method.

RESULTS: Nicotine pretreatment significantly attenuated the severity of lung injury and inhibited the production of TNF-alpha, IL-1beta and HMGB-1 in mice with ALI. After LPS administration, the lung wet/dry weight ratios, as an index of lung edema, and MPO activity were also markedly reduced by nicotine pretreatment. Early treatment with a high dose of nicotine (500 mug/kg) after LPS administration decreased the mortality in mice with ALI, even when treatment was started 24 h after LPS administration.

CONCLUSION: Nicotine attenuated the lung injury and reduced mortality in mice with LPS-induced ALI.