Tobaksrökens effekter på den lymfocytrekryterande cytokinen interleukin-16

Sammanfattning: 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.