Protective effect of nicotine on lipopolysaccharide-induced acute lung injury in mice.
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.
Ni
Yun Feng
YF
Department of Thoracic Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
Tian
Feng
F
Lu
Zi Fan
ZF
Yang
Guo Dong
GD
Fu
Hai Yan
HY
Wang
Jian
J
Yan
Xiao Long
XL
Zhao
Ya Chao
YC
Wang
Yun Jie
YJ
Jiang
Tao
T
D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000401:mortality / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D004926:Escherichia coli; D024243:HMGB1 Protein / Q000276:immunology; D007322:Instillation, Drug; D053583:Interleukin-1beta / Q000276:immunology; D053208:Kaplan-Meier Estimate; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009538:Nicotine / Q000276:immunology / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D024243:HMGB1 Protein; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D020011:Protective Agents; D014409:Tumor Necrosis Factor-alpha; D009538:Nicotine; D009195:Peroxidase