title: Nicotine exerts an anti-inflammatory effect in a murine model of acute lung injury.
abstract: 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.
authors.affiliation: School of Pharmacy & Biomolecular Sciences, University of Brighton, Brighton BN2 4GJ, UK. j.g.Mabley@brighton.ac.uk
authors.forename: Jon
authors.initials: J
authors.lastname: Mabley
authors.forename: Sevelanne
authors.initials: S
authors.lastname: Gordon
authors.forename: Pal
authors.initials: P
authors.lastname: Pacher
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D018925:Chemokines / Q000096:biosynthesis / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D004487:Edema; D005731:Ganglionic Stimulants / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000276:immunology; D051379:Mice; D009538:Nicotine / Q000627:therapeutic use*; D009195:Peroxidase / Q000096:biosynthesis / Q000187:drug effects; D011014:Pneumonia / Q000188:drug therapy*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D005731:Ganglionic Stimulants; D008070:Lipopolysaccharides; D009538:Nicotine; D009195:Peroxidase