Induction of pro-inflammatory cytokine release by human macrophages during exposure of Streptococcus pneumoniae to penicillin is influenced by minimum inhibitory concentration ratio

• Published in: International journal of antimicrobial agents 2005-09, Vol.26 (3), p.188-196
• Main Authors: Moore, Lisa J., Pridmore, Alison C., Lee, Margaret E., Read, Robert C.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Cells, Cultured; Cytokines - genetics; Cytokines - metabolism; Enzyme-Linked Immunosorbent Assay; Gene Expression; Humans; IL-1β; Inflammation; Interleukin-1 - genetics; Interleukin-1 - metabolism; Macrophages - immunology; Medical sciences; Microbial Sensitivity Tests; Microscopy, Electron, Scanning; Penicillin; Penicillins - pharmacology; Pharmacology. Drug treatments; Polymerase Chain Reaction; RNA, Messenger - analysis; Streptococcus pneumoniae; Streptococcus pneumoniae - drug effects; Streptococcus pneumoniae - immunology; TNF-α; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2005.06.006

β-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-α (TNF-α) and interleukin-1β (IL-1β) 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-α messenger RNA (mRNA), but not TNF-α protein at 6 h compared with untreated bacteria. IL-1β 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-1β. 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.