title: Combustible and non-combustible tobacco product preparations differentially regulate human peripheral blood mononuclear cell functions.
abstract: 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 preparations of cigarette smoke, ST extract 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 in complete artificial saliva (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-γ and TNF-α was evident in NK cells and T cells treated with WS-CM and TPM. Consistently, attenuation of ligand-induced secretion of cytokines (IL-1β, IL-10, IL-12 and TNF-α) from PBMCs treated with WS-CM and TPM were observed. While the treatment with TPPs did not alter the expression of the maturation marker CD69, WS-CM and TPM inhibited the cytolytic activity of human PBMCs. Suppression of perforin by WS-CM was also 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.
authors.affiliation: Department of Microbiology & Immunology, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA. sarimill@wakehealth.edu
authors.forename: Subhashini
authors.initials: S
authors.lastname: Arimilli
authors.forename: Brad E
authors.initials: BE
authors.lastname: Damratoski
authors.forename: G L
authors.initials: GL
authors.lastname: Prasad
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides; D009538:Nicotine / Q000633:toxicity*; D054353:Perforin / Q000276:immunology; D011070:Poly I-C; D012463:Saliva; D012906:Smoke / Q000009:adverse effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D062789:Tobacco Products / Q000633:toxicity*; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D037181:Lectins, C-Type; D008070:Lipopolysaccharides; D009538:Nicotine; D054353:Perforin; D011070:Poly I-C; D012906:Smoke; D000099192:CD69 Antigens
keywords: Cytotoxicity assay; EC(50); LPS; NK cells; PBMCs; Poly I:C; T cells; Tobacco product preparations (TPPs)