title: Exposure to cigarette smoke, a major risk factor for sudden infant death syndrome: effects of cigarette smoke on inflammatory responses to viral infection and bacterial toxins.
abstract: Exposure to cigarette smoke is a major risk factor for sudden infant death syndrome and also for respiratory infections in children. It has been suggested that toxigenic bacteria colonizing the respiratory tract might play a role in some cases of sudden infant death syndrome and nicotine has been demonstrated to enhance the lethality of bacterial toxins in a model system. Pyrogenic toxins of Staphylococcus aureus have been identified in tissues of infants who died of sudden infant death syndrome. It has been suggested that some of these deaths were due to induction of inflammatory mediators by infectious agents during a period when infants are less able to control these responses. The aim of this study was to assess the effects of a water-soluble cigarette smoke extract on the production of tumor necrosis factor alpha and nitric oxide from human monocytes in response to staphylococcal toxic shock syndrome toxin 1 or infection of the monocytes with respiratory syncytial virus. Cell culture supernatants were examined by a bioassay using mouse fibroblasts (L-929 cell line) for tumor necrosis factor alpha activity and by a spectrophotometric method for nitrite. Compared with monocytes incubated with medium only, monocytes incubated with any of the factors or their combinations tested in the study released higher levels of tumor necrosis factor alpha and lower levels of nitric oxide. Incubation with cigarette smoke extract increased tumor necrosis factor alpha from respiratory syncytial virus-infected cells while it decreased tumor necrosis factor alpha from cells incubated with toxic shock syndrome toxin. Incubation with cigarette smoke extract decreased the nitric oxide production from respiratory syncytial virus-infected cells while it increased the nitric oxide production from cells incubated with toxic shock syndrome toxin. Monocytes from a minority of individuals demonstrated extreme tumor necrosis factor alpha responses and/or very high or very low nitric oxide. The proportion of samples in which extreme responses with a very high tumor necrosis factor alpha and very low nitric oxide were detected was increased in the presence of the three agents to 20% compared with 0% observed with toxic shock syndrome toxin 1 or 4% observed with cigarette smoke extract or respiratory syncytial virus.
authors.affiliation: Department of Medical Microbiology, University of Edinburgh, Medical School, UK. m.raza@ed.ac.uk
authors.forename: M W
authors.initials: MW
authors.lastname: Raza
authors.forename: S D
authors.initials: SD
authors.lastname: Essery
authors.forename: R A
authors.initials: RA
authors.lastname: Elton
authors.forename: D M
authors.initials: DM
authors.lastname: Weir
authors.forename: A
authors.initials: A
authors.lastname: Busuttil
authors.forename: C
authors.initials: C
authors.lastname: Blackwell
mesh_terms: D000818:Animals; D001427:Bacterial Toxins; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology*; D006801:Humans; D007231:Infant, Newborn; D051379:Mice; D009000:Monocytes / Q000276:immunology / Q000378:metabolism* / Q000821:virology*; D009569:Nitric Oxide / Q000096:biosynthesis; D010947:Plants, Toxic; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D012307:Risk Factors; D012906:Smoke / Q000009:adverse effects*; D013398:Sudden Infant Death / Q000209:etiology* / Q000276:immunology; D018089:Superantigens; D014026:Nicotiana; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D012906:Smoke; D018089:Superantigens; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D009569:Nitric Oxide