Inflammatory changes in the airways of mice caused by cigarette smoke exposure are only partially reversed after smoking cessation.
BACKGROUND
Tobacco smoking irritates and damages the respiratory tract and contributes to a higher risk of developing lung emphysema. At present, smoking cessation is the only effective treatment for reducing the progression of lung emphysema, however, there is hardly anything known about the effects of smoking cessation on cytokine and chemokine levels in the airways. To the best of our knowledge, this is the first reported in vivo study in which cytokine profiles were determined after cessation of cigarette smoke exposure.


METHODS
The severity of airway remodeling and inflammation was studied by analyzing alveolar enlargement, heart hypertrophy, inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung tissue and by determining the cytokine and chemokine profiles in the BALF of A/J mice exposed to cigarette smoke for 20 weeks and 8 weeks after smoking cessation.


RESULTS
The alveolar enlargement and right ventricle heart hypertrophy found in smoke-exposed mice remained unchanged after smoking cessation. Although the neutrophilic inflammation in the BALF of cigarette smoke-exposed animals was reduced after smoking cessation, a sustained inflammation in the lung tissue was observed. The elevated cytokine (IL-1 alpha and TNF-alpha) and chemokine (CCL2 and CCL3) levels in the BALF of smoke-exposed mice returned to basal levels after smoking cessation, while the increased IL-12 levels did not return to its basal level. The cigarette smoke-enhanced VEGF levels did not significantly change after smoking cessation. Moreover, IL-10 levels were reduced in the BALF of smoke-exposed mice and these levels were still significantly decreased after smoking cessation compared to the control animals.


CONCLUSIONS
The inflammatory changes in the airways caused by cigarette smoke exposure were only partially reversed after smoking cessation. Although smoking cessation should be the first step in reducing the progression of lung emphysema, additional medication could be provided to tackle the sustained airway inflammation.
Braber
Saskia
S
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands. s.braber@uu.nl
Henricks
Paul A J
PA
Nijkamp
Frans P
FP
Kraneveld
Aletta D
AD
Folkerts
Gert
G
D056151:Airway Remodeling; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D018932:Chemokine CCL2 / Q000378:metabolism; D054405:Chemokine CCL3 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D017380:Hypertrophy, Right Ventricular / Q000276:immunology / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism*; D053582:Interleukin-1alpha / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008176:Lung Volume Measurements; D051379:Mice; D011014:Pneumonia / Q000276:immunology* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index; D012907:Smoking / Q000009:adverse effects*; D016540:Smoking Cessation; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C491768:Ccl2 protein, mouse; C496534:Ccl3 protein, mouse; D018932:Chemokine CCL2; D054405:Chemokine CCL3; D018836:Inflammation Mediators; D053582:Interleukin-1alpha; D014409:Tumor Necrosis Factor-alpha