title: Differential roles of interleukin-18 (IL-18) and IL12 for induction of gamma interferon by staphylococcal cell wall components and superantigens.
abstract: The roles of endogenous cytokines induced by either intact staphylococcal microorganisms or staphylococcal exotoxins were examined using human whole-blood cultures. To accomplish this, interleukin-18 binding protein (IL-18BP) and tumor necrosis factor binding protein (TNFbp) were used to neutralize IL-18 and TNF, respectively, whereas an anti-IL-12 monoclonal antibody was used to neutralize IL-12 and the IL-1 receptor antagonist (IL-1Ra) was used to block IL-1 receptors. Heat-killed Staphylococcus epidermidis and Staphylococcus aureus, as well as the staphylococcal superantigens toxic shock syndrome toxin-1 (TSST-1) and staphylococcus enterotoxin B (SEB) induced gamma interferon (IFN-gamma) production. Staphylococcus spp.-induced production of IFN-gamma required the presence of endogenous IL-18, IL-12, and TNF. In contrast, TSST-1-induced IFN-gamma was not significantly reduced in the presence of IL-18BP, anti-IL-12 antibodies, IL-1Ra, or anti-TNFbp. SEB-induced IFN-gamma was significantly inhibited only by anti-IL-12 antibodies, indicating that endogenous IL-18, IL-1, and TNF are not required for SEB-induced IFN-gamma. In conclusion, the mechanisms of IFN-gamma stimulation by intact staphylococcal microorganisms and by exotoxins differ, and this is likely due to the different receptors which are triggered on the cell membranes. In contrast to its role in the interactions between staphylococci and host cells, IL-18 does not appear to play a major role in superantigen-induced IFN-gamma.
authors.affiliation: Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Stuyt
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.forename: D
authors.initials: D
authors.lastname: Novick
authors.forename: M
authors.initials: M
authors.lastname: Rubinstein
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: J W
authors.initials: JW
authors.lastname: Van der Meer
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins; D002473:Cell Wall / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D010457:Peptidoglycan / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*; D013212:Staphylococcus epidermidis / Q000276:immunology*; D018089:Superantigens / Q000276:immunology; D013682:Teichoic Acids / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D020382:Interleukin-18; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D018089:Superantigens; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal; D018664:Interleukin-12; C031818:enterotoxin B, staphylococcal; C009900:lipoteichoic acid; D007371:Interferon-gamma