Acute pulmonary effects of aerosolized nicotine

Am J Physiol Lung Cell Mol Physiol. 2019 Jan 1;316(1):L94-L104. doi: 10.1152/ajplung.00564.2017. Epub 2018 Oct 25.


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 μm) in the respirable diameter range. Acute nicotine inhalation caused increased pulmonary edema and lung injury as measured by enhanced bronchoalveolar lavage fluid 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 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-1α 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 transepithelial electrical resistance 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.

Keywords: aerosol; lung injury; nicotine; pulmonary edema; rats.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerosols
  • Animals
  • Blood-Air Barrier* / injuries
  • Blood-Air Barrier* / metabolism
  • Blood-Air Barrier* / pathology
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Chemokine CXCL1 / blood
  • HMGB1 Protein / metabolism
  • Immunoglobulin M / blood
  • Interleukin-1alpha / blood
  • Leukocyte Count
  • Male
  • Neutrophil Infiltration / drug effects
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Nicotine / adverse effects*
  • Nicotine / pharmacology
  • Particle Size
  • Pulmonary Edema / blood
  • Pulmonary Edema / chemically induced
  • Pulmonary Edema / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Vaping* / adverse effects
  • Vaping* / blood
  • Vaping* / pathology


  • Aerosols
  • Chemokine CXCL1
  • Cxcl1 protein, rat
  • HMGB1 Protein
  • Hbp1 protein, rat
  • Immunoglobulin M
  • Interleukin-1alpha
  • Nicotine
  • Casp3 protein, rat
  • Caspase 3
  • Caspase 7
  • Casp7 protein, rat