title: Induction of pro-inflammatory cytokine release by human macrophages during exposure of Streptococcus pneumoniae to penicillin is influenced by minimum inhibitory concentration ratio.
abstract: beta-Lactam antibiotics cause release of pro-inflammatory bacterial cell wall structures. We determined the effect of penicillin treatment of Streptococcus pneumoniae on the induction of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) genes by human macrophages and the influence of antibiotic concentration and bacterial growth phase upon this induction. Gene expression was measured by real-time polymerase chain reaction (PCR) and protein was measured by enzyme-linked immunosorbent assay (ELISA). Treatment of lag phase S. pneumoniae with one-eighth minimum inhibitory concentration (MIC) penicillin resulted in enhanced expression of TNF-alpha messenger RNA (mRNA), but not TNF-alpha protein at 6h compared with untreated bacteria. IL-1beta mRNA and protein were not affected by these bacteria. MIC treatment of lag or early log phase bacteria induced both protein and mRNA for IL-1beta. Bacteria exposed to concentrations of penicillin that cause lysis (MIC) or no lysis with morphological changes (sub-MIC) induce differential patterns of pro-inflammatory cytokine expression by human macrophages.
authors.affiliation: Division of Genomic Medicine, University of Sheffield School of Medicine and Biomedical Sciences, Beech Hill Road, Sheffield S10 2RX, UK.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Moore
authors.forename: Alison C
authors.initials: AC
authors.lastname: Pridmore
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Lee
authors.forename: Robert C
authors.initials: RC
authors.lastname: Read
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology*; D008826:Microbial Sensitivity Tests; D008855:Microscopy, Electron, Scanning; D010406:Penicillins / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D007375:Interleukin-1; D010406:Penicillins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha