Impairment of human NK cell cytotoxic activity and cytokine release by cigarette smoke

NK cells play essential roles in innate host defense against microbial infections and tu- mor surveillance. Although evidence suggests that smoking has adverse effects on the immune system, little is known about whether smoking compro- mises NK cell effector functions. In this study, we show that cigarette smoke-conditioned medium (SCM) dose-dependently inhibits in vitro IFN- production by polyinosinic:polycytidylic acid (poly I:C)-activated PBMC and NK cells isolated from nonsmoking individuals. Similarly, SCM attenuated poly I:C-induced TNF- production by PBMC and NK cells. The inhibitory effect of cigarette smoke on TNF- production was reversible. PBMC and NK cells isolated from smokers displayed signifi- cant reduction of IFN- and TNF- secretions compared with nonsmokers in response to poly I:C activation. We further observed that SCM attenu- ated NK cell cytotoxic activity, which was associ- ated with decreased up-regulation of perforin ex- pression. Attenuated cytotoxic activity was also ob- served in PBMCs isolated from smokers. Finally, anti-IL-12 mAb-blocking data revealed that an at- tenuation of IFN- production by PBMC was indi- rect, likely via attenuation of IL-12 production, and the effect on NK cells was IL-12-independent. Our data indicate that cigarette smoke compro- mises function of human NK cells. This may con- tribute to a higher incidence of viral infections and cancer among smokers. J. Leukoc. Biol. 83: 000-000; 2008.