Exposing rodents to a combination of tobacco smoke and lipopolysaccharide results in an exaggerated inflammatory response in the lung
Article first published online: 7 MAY 2010
© 2010 Novartis Pharmaceuticals UK. Journal compilation © 2010 The British Pharmacological Society
British Journal of Pharmacology
Volume 160, Issue 8, pages 1985–1996, August 2010
How to Cite
Hardaker, E., Freeman, M., Dale, N., Bahra, P., Raza, F., Banner, K. and Poll, C. (2010), Exposing rodents to a combination of tobacco smoke and lipopolysaccharide results in an exaggerated inflammatory response in the lung. British Journal of Pharmacology, 160: 1985–1996. doi: 10.1111/j.1476-5381.2010.00857.x
- Issue published online: 21 JUL 2010
- Article first published online: 7 MAY 2010
- Received; 15 July 2009; Revised; 5 March 2010; Accepted; 8 March 2010
- acute exacerbations;
- tobacco smoke;
- LPS, steroids;
- PDE4 inhibitors
BACKGROUND AND PURPOSE
Acute exacerbations of chronic obstructive pulmonary disease (COPD), which are often associated with respiratory infections, are defined as a worsening of symptoms that require a change in medication. Exacerbations are characterized by a reduction in lung function, quality of life and are associated with increased pro-inflammatory mediators in the lung. Our aim was to develop an animal model to mimic aspects of this exaggerated inflammatory response by combining key etiological factors, tobacco smoke (TS) and bacterial lipopolysaccharide (LPS).
Rats were exposed to TS for 30 min twice a day for 2 days. On day 3 animals were exposed to LPS for 30 min followed by exposure to TS 5 h later. Inflammation, mucus and lung function were assessed 24 h after LPS.
Neutrophils, mucus, oedema and cytotoxicity in lung and/or bronchoalveolar lavage was increased in animals exposed to combined LPS and TS, compared with either stimulus alone. Lung function was impaired in animals exposed to combined LPS and TS. Inflammatory cells, oedema and mucus were unaffected by pretreatment with the corticosteroid, budesonide, but were reduced by the phosphodiesterase 4 selective inhibitor roflumilast. Additionally, lung function was improved by roflumilast.
CONCLUSIONS AND IMPLICATIONS
We have established an in vivo model mimicking characteristic features of acute exacerbations of COPD including lung function decline and increased lung inflammation. This model may be useful to investigate molecular and cellular mechanisms underlying such exacerbations, to identify new targets and to discover novel therapeutic agents.