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

Abstract 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.