title: Differential effects of ethanol on IFN-gamma- and TNF-alpha-producing splenic T lymphocytes in a murine model of gram-negative pneumonia.
abstract: The incidence of bacterial pneumonia is increased in alcoholic patients. Alcohol consumption has been shown to impair cytokine production. Tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) are critical for host defense against Klebsiella pneumoniae (K. pneumoniae). In order to examine the influence of alcohol on the immune response to infection, we investigated the frequency of TNF-alpha and IFN-gamma produced by splenic T-lymphocytes in a murine model of gram-negative pneumonia initiated after 8 days of alcohol treatment. Thirty-two Balb/c mice were pretreated with ethanol (3 mg/g body weight) or saline intraperitoneally over 8 days. On day 7 half of each group was administered K. pneumoniae. Mice were sacrificed 24 hours later to excise lungs and liver for histological assessment and spleens for cell isolation. IFN-gamma- and TNF-alpha-producing CD4(+) and CD8(+) lymphocytes were determined by FACS analysis. In mice with Klebsiella infection, the percentages of IFN-gamma-producing CD4(+) (P < 0.01) and CD8(+) (P < 0.01) were significantly decreased, the percentages of TNF-alpha-producing CD4(+) (P = 0.01) and CD8(+) (P < 0.01) T cells were significantly elevated after alcohol treatment compared with mice with saline treatment. The histological assessment showed an aggravation of K. pneumoniae-induced pneumonia in alcohol-treated mice. Alcohol differentially affects IFN-gamma and TNF-alpha production in Klebsiella-infected mice. Both effects obviously led to a weakened immune response as seen by increased histological damage. This suggests a role of T cells in the increased susceptibility of the alcoholic host to nosocomial infection due to inadequate cytokine response.
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Charité Campus Mitte and Campus Virchow-Klinikum, Charité Universitätsmedizin Berlin, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Lanzke
authors.forename: Robin
authors.initials: R
authors.lastname: Kleinwächter
authors.forename: Saskia
authors.initials: S
authors.lastname: Kerschischnik
authors.forename: Lilit
authors.initials: L
authors.lastname: Sargsyan
authors.forename: David A
authors.initials: DA
authors.lastname: Groneberg
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
authors.forename: Oliver
authors.initials: O
authors.lastname: Liesenfeld
authors.forename: Veit
authors.initials: V
authors.lastname: Krenn
authors.forename: Michael
authors.initials: M
authors.lastname: Sander
authors.forename: Claudia
authors.initials: C
authors.lastname: Spies
mesh_terms: D000435:Alcoholic Intoxication / Q000276:immunology / Q000473:pathology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000097:blood*; D007710:Klebsiella Infections / Q000276:immunology* / Q000473:pathology; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008099:Liver / Q000276:immunology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D000431:Ethanol; D007371:Interferon-gamma