title: Reduction in cytokine release from human monocytes by modifications in cell wall structure of Staphylococcus aureus induced by subinhibitory concentrations of oxacillin.
abstract: Whole bacterial cells of Staphylococcus aureus as well as purified staphylococcal peptidoglycan (PG) have been demonstrated to stimulate human monocytes to release cytokines. Hypothesising that the phenomenon of changes induced by beta-lactam antibiotics in cell-wall composition may alter the immunological properties of the intact cell wall as well as of purified cell-wall components, this study assessed whether cytokine release by human monocytes is altered if cells from strains grown in the presence or absence of sub-minimal inhibitory concentrations of oxacillin are used as stimuli. Whole bacterial cells and isolated PG from these strains, grown in the presence of oxacillin, showed a significantly reduced stimulation of tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6 release by human monocytes in a concentration-dependent fashion. The serum-induced potentiation of cytokine production by human monocytes in response to PG with modified cross-linking was also reduced. These observations may have particular relevance for staphylococcal infections, in which clinically achievable beta-lactam concentrations do not suppress staphylococcal growth yet may alter and possibly enhance virulence.
authors.affiliation: Institute for Medical Microbiology and Virology, Heinrich-Heine University Düsseldorf, Germany.
authors.forename: F J
authors.initials: FJ
authors.lastname: Schmitz
authors.forename: J
authors.initials: J
authors.lastname: Verhoef
authors.forename: U
authors.initials: U
authors.lastname: Hadding
authors.forename: H P
authors.initials: HP
authors.lastname: Heinz
authors.forename: M E
authors.initials: ME
authors.lastname: Jones
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002473:Cell Wall / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D010068:Oxacillin / Q000008:administration & dosage / Q000494:pharmacology*; D010406:Penicillins / Q000008:administration & dosage / Q000494:pharmacology*; D010457:Peptidoglycan / Q000302:isolation & purification / Q000494:pharmacology; D013203:Staphylococcal Infections / Q000209:etiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000276:immunology* / Q000472:pathogenicity; D013682:Teichoic Acids / Q000302:isolation & purification / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014774:Virulence / Q000187:drug effects / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D010406:Penicillins; D010457:Peptidoglycan; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; D010068:Oxacillin