TSRC, Tob. Sci. Res. Conf., 2013, 67, abstr. 19

Tobacco product preparations differentially regulate human PBMC functions, including T cell and NK function.

(1) Wake Forest University School of Medicine, Winston-Salem, NC, USA; (2) Reynolds Tobacco Company, Winston-Salem, NC, USA

Natural Killer (NK) cells and T cells play essential roles in innate and adaptive immune responses in protecting against microbial infections and in tumor surveillance. Although evidence suggests that smoking causes immunosuppression, there is limited information whether the use of smokeless tobacco (ST) products affects immune responses. In this study, we assessed the effects of two cigarette smoke preparations, ST and nicotine on T cell and NK cell responses using Toll-like receptor-ligand stimulated human peripheral blood mononuclear cells (PBMCs). The tobacco product preparations (TPPs) tested included whole smoke conditioned media (WS-CM), total particulate matter (TPM) and a ST product preparation (ST/CAS). The PBMCs were stimulated with polyinosinic:polycytidylic acid (poly I:C) and lipopolysaccharide (LPS). A marked reduction of the expression of intracellular IFN-g and TNF-a was evident in NK cells and T cells treated with WS-CM and TPM. Consistently, attenuation of ligand induced secretion of cytokines (IL-1b, IL-10, IL-12 and TNF-a from PBMCs treated with WS-CM and TPM were observed. WS-CM and TPM also inhibited the cytolytic activity of human PBMCs. Significant suppression of perforin in PBMCs and in NK cells by WS-CM was detected. Although interference from the vehicle confounded the interpretation of effects of ST/CAS, some effects were evident only at high concentrations. Nicotine treatment minimally impacted expression of cytokines and cytolytic activity. Data presented herein suggests that the function of NK cells and T cells is influenced by exposure to TPPs (based on equi- nicotine units) in the following order: WS-CM>TPM>ST/CAS. These findings are consistent with the hypothesis put forward by others that chronic smoking leads to immunosuppression, an effect that may contribute to increased microbial infections and cancer incidence among smokers.