Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers with and without COPD

Abstract

BackgroundLong-term exposure to tobacco smoke causes local inflammation in the airways that involves not only innate immune cells, including NK cells, but also adaptive immune cells such as cytotoxic (CD8+) and helper (CD4+) T-cells. We have previously demonstrated that long-term tobacco smoking increases extracellular concentration of the CD4+-recruiting cytokine interleukin (IL)-16 locally in the airways. Here, we hypothesized that tobacco smoking alters IL-16 biology at the systemic level and that this effect involves oxygen free radicals (OFR).MethodsWe quantified extracellular IL-16 protein (ELISA) and intracellular IL-16 in NK cells, T-cells, B-cells, and monocytes (flow cytometry) in blood samples from long-term tobacco smokers with and without chronic obstructive pulmonary disease (COPD) and in never-smokers. NK cells from healthy blood donors were stimulated with water-soluble tobacco smoke components (cigarette smoke extract) with or without an OFR scavenger (glutathione) in vitro and followed by quantification of IL-16 protein.ResultsThe extracellular concentrations of IL-16 protein in blood did not display any substantial differences between groups. Notably, intracellular IL-16 protein was detected in all types of blood leukocytes. All long-term smokers displayed a decrease in this IL-16 among NK cells, irrespective of COPD status. Further, both NK and CD4+ T-cell concentrations displayed a negative correlation with pack-years. Moreover, cigarette smoke extract caused release of IL-16 protein from NK cells in vitro, and this was not affected by glutathione, in contrast to the decrease in intracellular IL-16, which was prevented by this drug.ConclusionLong-term exposure to tobacco smoke does not markedly alter extracellular concentrations of IL-16 protein in blood. However, it does decrease the intracellular IL-16 concentrations in blood NK cells, the latter effect involving OFR. Thus, long-term tobacco smoking exerts an impact at the systemic level that involves NK cells; innate immune cells that are critical for host defense against viruses and tumors – conditions that are overrepresented among smokers.

Association of mean platelet volume with incident type 2 diabetes mellitus risk: the Dongfeng–Tongji cohort study

“…In the present study we found that the positive association of higher MPV and DM incidence was more pronounced in non-current smokers. Smoking was positively associated with increased MPV levels [ 36 ], inflammation [ 37 ] and immune response [ 38 ]. High levels of inflammation in current smokers and relative higher ratio of females in the non-smokers compared to the current smokers (69.2% vs. 6.7%) might contribute to the smoking-MPV interaction on incident DM risk.…”

Tobacco Smoke Induces and Alters Immune Responses in the Lung Triggering Inflammation, Allergy, Asthma and Other Lung Diseases: A Mechanistic Review

“…NK cells from long-term smokers display a decreased intracellular IL-16 concentration. This depletion of the CD4+-recruiting cytokine strongly suggests that long-term smoking may impact immune responses at the systemic level, and that NK cells are involved [ 250 ]. There is ample evidence showing direct negative effect of cigarette smoke on NK cell cytolytic capacity, as well as on their ability to produce inflammatory cytokines in response to microbial agents.…”

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“…Our research group has previously characterized systemic neutrophil mobilization, the CXC chemokine, the growth related oncogene-alpha (GRO-α) and interleukin(IL)-17A (formerly known as IL-17) in COPD during stable disease and exacerbations. [30][31][32] At this systemic level, the average IL-17A concentration during stable disease is substantially lower in smokers with COPD than in controls, especially in the smokers with COPD whose lungs have been colonized by airway pathogens. 30 The long-term alterations in IL-17 levels in COPD patients have not been studied.…”