Protective effect of nicotine on lipopolysaccharide-induced acute lung injury in mice.
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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 μg/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)-α, interleukin (IL)-1β 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-α, IL-1β 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 μg/kg) after LPS administration decreased the mortality in mice with ALI, even when treatment was started 24 h after LPS administration.
CONCLUSIONS
Nicotine attenuated the lung injury and reduced mortality in mice with LPS-induced ALI.
