Tobaksrökens effekter på den lymfocytrekryterande cytokinen interleukin-16
The Effects of Tobacco Smoke on the Lymphocyte Recruiting Cytokine Interleukin-16
Background: There is an increased number of CD8+ cells in the airways in chronic obstructive pulmonary disease (COPD) and also an increased number of CD4+ cells in severe COPD. The CD4 cell chemoattractant interleukin (IL)-16 is also increased in the airways of tobacco smokers. In this thesis, we re-evaluated whether there is a local increase in IL-16 and determined whether there are systemic IL-16 alterations. We also investigated whether tobacco smoke causes a release of IL-16 in CD8+ cells and elucidated cellular mechanisms. Methods: We measured extracellular IL-16 protein (bronchoalveolar lavage fluid, BALF; plasma and serum), intracellular IL-16 protein (BAL CD8+ cells) and IL-16 mRNA (BAL cells) in long-term tobacco smokers. In occasional tobacco smokers, we analysed extracellular IL-16 protein (BALF). IL-16 protein in tonsils of tobacco smokers was assessed. For the in vitro studies, isolated human blood CD8+ cells were cultivated with and without water-soluble tobacco smoke components (CSE), an oxygen free radical (OFR) scavenger (glutathione) or a non-selective phosphodiesterase inhibitor (aminophylline) and analysed for extra- and intracellular IL-16 protein and IL-16 mRNA. Protein oxidation in CSE-treated CD8+ cells was also measured. Results: In long-term tobacco smokers, we confirmed an increase in IL-16 protein in BALF. We revealed a decrease in intracellular IL-16 protein in CD8+ cells as well as in IL16 mRNA in BAL cells. We found no corresponding impact on IL-16 protein in plasma or serum. In contrast, occasional smokers did not exhibit any substantial alteration in IL-16 protein in BALF. However, tobacco smokers were found to have a decrease in IL-16 in tonsils. In cell culture of CD8+ cells, CSE caused a release of IL-16 protein and a decrease in both intracellular IL-16 protein and IL-16 mRNA. These alterations were prevented by glutathione but not by aminophylline. CSE-treated CD8+ cells exhibited a marked increase in oxidized proteins. Conclusion: Tobacco smoke mainly exerts an effect on IL-16 release locally in the airways. CD8+ cells constitute a source of IL-16 and tobacco smoke depletes these cells by causing an extracellular release of this protein and a decrease in its mRNA. OFRs are involved as mediators of these effects.
Parts of work
1. A. Andersson, I. Qvarfordt, M. Laan, M. Sjöstrand, C. Malmhäll, G. C. Riise, L.-O. Cardell and A. Lindén Impact of tobacco smoke on interleukin-16 protein in human airways, lymphoid tissue and T lymphocytes Clinical and Experimental Immunology, 2004 Oct;138(1):75-82. ::doi::10.1111/j.1365-2249.2004.02580.x2. A. Andersson, A. Bossios, C. Malmhäll, M. Sjöstrand, M. Eldh, B-M. Eldh, P. Glader, B. Andersson, I. Qvarfordt, G.C. Riise and A. Lindén Effects of tobacco smoke on IL-16 in CD8+ cells from human airways and blood: a key role for oxygen free radicals? American Journal of Physiology, Lung Cellular and Molecular Physiology 2011 Jan;300(1):L43-55. ::doi::10.1152/ajplung.00387.20093. A. Andersson *), A. Bossios *), C. Malmhäll, B. Houltz, M. Sjöstrand, I. Qvarfordt and A. Lindén Decrease in Interleukin-16-expressing NK cells in the Blood of Long-Term Tobacco Smokers Manuscript.
University of Gothenburg. Sahlgrenska Academy
Institute of Medicine. Department of Internal Medicine
Fredagen den 18:e november 2011, kl. 13, Hjärtats aula, Vita Stråket 12, Sahlgrenska sjukhuset
Date of defence