Vitamin D deficiency exacerbates COPD-like characteristics in the lungs of cigarette smoke-exposed mice
Respiratory Research 2015, 16:110 doi:10.1186/s12931-015-0271-x
Nele Heulens1†, Hannelie Korf2†, Nele Cielen1, Elien De Smidt2, Karen Maes1, Conny Gysemans2, Erik Verbeken3, Ghislaine Gayan-Ramirez1, Chantal Mathieu2† and Wim Janssens1 wim.janssens@uzleuven.be † † Equal contributors
1 Laboratory of Respiratory Diseases, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, Leuven, 3000, Belgium
2 Laboratory of Clinical and Experimental Endocrinology, Department of Clinical and Experimental Medicine, Katholieke Universiteit Leuven, Herestraat 49, Leuven, 3000, Belgium
3 Translational Cell and Tissue Research, Department of Imaging and Pathology, Katholieke Universiteit Leuven, Minderbroederstraat 12, Leuven, 3000, Belgium
| Vitamin D deficient diet | <100 IU /kg of feed | 17–20 ng/ml. |
| Control diet | 1000 IU /kg of feed | 75–90 ng/ml |
Mice exposed to the smoke were second generation mice on the diet
Mice with ~20 ng had far more lung problems than those with ~ 80 ng
From Background
Chronic obstructive pulmonary disease (COPD) is a chronic disease characterized by a progressive expiratory airflow limitation and is associated with chronic inflammation in the airways and lung parenchyma . In the majority of cases, this inflammatory response in COPD is initiated by long-term exposure to cigarette smoke (CS), which triggers a series of events that damage the airways and terminal airspaces, leading to lung function decline and emphysema.
A great many charts and microphotographs in the PDF
Download the PDF from VitaminDWiki
See also VitaminDWiki
- Smoking reduces vitamin D - many studies , vs this study shows problems if ALREADY have low vitamin D. Note – this study did not test vitamin D levels AFTER the smoke
- COPD fought by Vitamin D - many studies
- COPD reduced by 40 percent with monthly 100,000 IU of vitamin D – RCT Jan 2015
- COPD becoming suddenly worse is 30X more likely if low vitamin D – Dec 2014
- COPD – almost all women in Bulgaria hospitalized with COPD had low vitamin D – June 2015
- Search VitaminDWiki for COPD 338 items as of Dec 2014
Background
Chronic obstructive pulmonary disease (COPD) is characterized by excessive inflammation and disturbed bacterial clearance in the airways. Although cigarette smoke (CS) exposure poses a major risk, vitamin D deficiency could potentially contribute to COPD progression. Many in vitro studies demonstrate important anti-inflammatory and antibacterial effects of vitamin D, but a direct contribution of vitamin D deficiency to COPD onset and disease progression has not been explored.
Methods
In the current study, we used a murine experimental model to investigate the combined effect of vitamin D deficiency and CS exposure on the development of COPD-like characteristics. Therefore, vitamin D deficient or control mice were exposed to CS or ambient air for a period of 6 (subacute) or 12 weeks (chronic). Besides lung function and structure measurements, we performed an in depth analysis of the size and composition of the cellular infiltrate in the airways and lung parenchyma and tested the ex vivo phagocytic and oxidative burst capacity of alveolar macrophages.
Results
Vitamin D deficient mice exhibited an accelerated lung function decline following CS exposure compared to control mice. Furthermore, early signs of emphysema were only observed in CS-exposed vitamin D deficient mice, which was accompanied by elevated levels of MMP-12 in the lung. Vitamin D deficient mice showed exacerbated infiltration of inflammatory cells in the airways and lung parenchyma after both subacute and chronic CS exposure compared to control mice. Furthermore, elevated levels of typical proinflammatory cytokines and chemokines could be detected in the bronchoalveolar lavage fluid (KC and TNF-α) and lung tissue (IP-10, MCP-1, IL-12) of CS-exposed vitamin D deficient mice compared to control mice. Finally, although CS greatly impaired the ex vivo phagocytic and oxidative burst function of alveolar macrophages, vitamin D deficient mice did not feature an additional defect.
Conclusions
Our data demonstrate that vitamin D deficiency both accelerates and aggravates the development of characteristic disease features of COPD. As vitamin D deficiency is highly prevalent, large randomized trials exploring effects of vitamin D supplementation on lung function decline and COPD onset are needed.