Tobacco smoke causes release of IL-16 protein from NK cells in vitro

Abstract

Background: The inflammatory process in chronic obstructive pulmonary disease (COPD) involves among other cells natural killer (NK) cells. Previous studies show that NK cells in smokers display a reduced cytotoxic capacity. Moreover, the cytokine interleukin (IL) -16 may modulate inflammatory responses both at extracellular and intracellular level. Extracellular IL-16 is a potent chemoattractant for CD4+ cells. These cells may be increased in the lower airways of tobacco smokers. In addition, intracellular IL-16 influences T cell cycle progression. Less is known of its role in NK cells but we have previously reported a reduced number of circulating IL-16+NK cells in smokers. Aims: To determine whether tobacco smoke is able to release IL-16 protein from NK cells in vitro. Methods: We isolated NK cells (CD3-CD16+CD56+) from buffy coat from clinically healthy blood donors using negative isolation by magnetic labeling. The isolated cells were cultured for 20 hours with or without cigarette smoke extract (CSE; concentration1:25). The concentration of extracellular IL-16 protein in conditioned medium was measured by ELISA. We also assessed the viability using exclusion of trypan blue after the culture. Results: The concentrations of IL-16 protein from CSE stimulated cells were 803 pg/ml (281-1100) compared with un-stimulated cells (vehicle) 40 pg/ml (8-87) [median (range)]. The viability was 97% (93-99) for CSE stimulated cells [median (range)] and 100% for vehicle. N=4. Conclusions: Tobacco smoke causes release of IL-16 protein from NK cells and we speculate that this effect leads to the decreased number of IL-16+NK cells observed in smokers, which may reflect an impaired ability to resist viruses and cancer tumors.