Acute pulmonary effects of aerosolized nicotine.

Nicotine is a highly addictive principal component of both tobacco and electronic cigarette that is readily absorbed in blood. Nicotine containing electronic cigarettes are promoted as a safe alternative to cigarette smoking. However, the isolated effects of inhaled nicotine are largely unknown. Here we report a novel rat model of aerosolized nicotine with a particle size (~1 micron) in the respirable diameter range. Acute nicotine inhalation caused increased pulmonary edema and lung injury as measured by enhanced bronchoalveolar lavage fluid (BALF) protein, IgM, lung wet-to-dry weight ratio and high mobility group box 1 (HMGB1) protein and decreased lung E-cadherin protein. Immunohistochemical analysis revealed congested blood vessels and increased neutrophil infiltration. Lung myeloperoxidase (MPO) mRNA and protein increased in the nicotine exposed rats. Complete blood counts also showed an increase in neutrophils, white blood cells, eosinophils and basophils. Arterial blood gas measurements showed an increase in lactate. Lungs of nicotine inhaling animals revealed increased mRNA levels of IL-1A and CXCL1. There was also an increase in IL-1a protein. In in vitro air-liquid interface cultures of airway epithelial cells there was a dose dependent increase in HMGB1 release with nicotine treatment. Air-liquid cultures exposed to nicotine also resulted in a dose-dependent loss of barrier as measured by trans-epithelial electrical resistance (TEER) and a decrease in E-cadherin expression. Nicotine also caused a dose dependent increase in epithelial cell death and an increase in caspase 3/7 activities. These results show that the nicotine content of electronic cigarettes may have adverse pulmonary and systemic effects.