Nicotine Exerts an Anti-inflammatory Effect in a Murine Model of Acute Lung Injury
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Activation of the cholinergic anti-inflammatory pathway through direct activation of nicotinic acetylcholine receptors on immune cells can inhibit pro-inflammatory chemokine and cytokine release and thereby protect in a variety of inflammatory diseases. The aim of this study was to investigate whether nicotine treatment protected against acute lung inflammation. Mice challenged with intratracheal lipopolysaccharide (LPS, 50 μg) were treated with nicotine (0.2 or 0.4 mg/kg, sc). After 24 h, bronchoalveolar lavage fluid (BALF) was obtained to measure leukocyte infiltration, lung edema, and pro-inflammatory chemokine (MIP-1α, MIP-2, and eotaxin) and cytokine (IL-1, IL-6, and TNF-α) levels. Nicotine treatment reduced the LPS-mediated infiltration of leukocytes and edema as evidenced by decreased BALF inflammatory cells, myeloperoxidase, and protein. Nicotine also downregulated lung production of pro-inflammatory chemokines and cytokines. These data support the proposal that activation of the cholinergic anti-inflammatory pathway may represent a useful addition to the therapy of acute respiratory distress syndrome.
KEY WORDSinflammation nicotine acetylcholine lung chemokine
- 22.Mishra, N.C., J. Rir-Sima-Ah, R.J. Langley, et al. 2008. Nicotine primarily suppresses lung Th2 but not goblet cell and muscle cell responses to allergens. Journal of Immunology 180: 7655–7663.Google Scholar
- 35.Yoshikawa, H., M. Kurokawa, N. Ozaki, et al. 2006. Nicotine inhibits the production of proinflammatory mediators in human monocytes by suppression of I-kappaB phosphorylation and nuclear factor-kappaB transcriptional activity through nicotinic acetylcholine receptor alpha7. Clinical and Experimental Immunology 146: 116–123.PubMedCrossRefGoogle Scholar
- 39.Abraham, E., J. Arcaroli, and R. Shenkar. 2001. Activation of extracellular signal-regulated kinases, NF-kappa B, and cyclic adenosine 5′-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia. Journal of Immunology 166: 522–530.Google Scholar