title: Development of an experimental model for assessing the effects of cigarette smoke and virus infections on inflammatory responses to bacterial antigens.
abstract: Interactions among major risk factors associated with bacterial infections were assessed in a model system using surrogates for virus infection; IFN-g, and exposure to cigarette smoke; cigarette smoke extract (CSE), nicotine and cotinine. Cytokine responses elicited by LPS from THP-1 cells in the presence of these components, or combinations of components, were assessed by multiplex bead assay, i.e. IL-1β, IL-6, IL-8, IL-10, TNF-α and IFN-γ. IFN-γ-priming significantly increased pro-inflammatory cytokines induced by LPS. CSE suppressed production of pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ, but enhanced production of IL-8. Nicotine and cotinine suppressed all cytokine responses. In combination, IFN-γ masked the inhibitory effects of CSE. In relation to the objectives of the study, we concluded that (a) IFN-γ at biologically relevant concentrations significantly enhanced pro-inflammatory responses; (b) CSE, nicotine and cotinine dysregulated the inflammatory response and that the effects of CSE were different from those of the individual components, nicotine and cotinine; (c) when both IFN-γ and CSE were present, IFN-γ masked the effect of CSE. There is a need for clinical investigations on the increase in IL-8 responses in relation to exposure to cigarette smoke and increased pro-inflammatory responses in relation to recent viral infection.
authors.affiliation: School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia Hunter Medical Research Institute, Newcastle, Australia.
authors.forename: Sophia
authors.initials: S
authors.lastname: Moscovis
authors.affiliation: Hunter Medical Research Institute, Newcastle, Australia Hunter Area Pathology Service Immunology, New Lambton, Australia.
authors.forename: Sharron
authors.initials: S
authors.lastname: Hall
authors.affiliation: Hunter Medical Research Institute, Newcastle, Australia Hunter Area Pathology Service Immunology, New Lambton, Australia.
authors.forename: Christine
authors.initials: C
authors.lastname: Burns
authors.affiliation: School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia Hunter Medical Research Institute, Newcastle, Australia Human Genetics, John Hunter Hospital, New Lambton, Australia.
authors.forename: Rodney
authors.initials: R
authors.lastname: Scott
authors.affiliation: School of Biomedical Sciences, Faculty of Health, University of Newcastle, Australia Hunter Medical Research Institute, Newcastle, Australia c_c_blackwell@hotmail.com.
authors.forename: Caroline
authors.initials: C
authors.lastname: Blackwell
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology*; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology; D003367:Cotinine / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D012906:Smoke / Q000009:adverse effects*; D062789:Tobacco Products; D014777:Virus Diseases / Q000276:immunology*; D014815:Vitamins / Q000494:pharmacology
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D008070:Lipopolysaccharides; D018722:Nicotinic Agonists; D012906:Smoke; D014815:Vitamins; D002762:Cholecalciferol; D009538:Nicotine; D007371:Interferon-gamma; D003367:Cotinine
keywords: Lipopolysaccharide; THP-1 cells; cigarette smoke; cytokine responses; virus infection