title: Effects of antibiotic class on the macrophage inflammatory response to Streptococcus pneumoniae.
abstract: Antibiotic choice can alter host inflammation during invasive bacterial infections. Previous studies of gram-negative organisms concluded that antibiotic-mediated release of bacterial cell wall components amplifies inflammation. Less has been reported about antibiotic effect on gram-positive organisms. This study explored the hypothesis that Streptococcus pneumoniae would induce greater macrophage inflammatory mediator production when killed with cell wall active antibiotics rather than protein synthesis inhibitors. Stimulation of RAW 264.7 murine macrophages with pneumococci and oxacillin led to significantly higher inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF) accumulation than did the same concentrations of pneumococci and clindamycin. Neither antibiotic alone or in combination with lipopolysaccharide acted directly on macrophages to modify the immune response. Endotoxin contamination did not confound the results, as preincubation with polymyxin B did not change iNOS or TNF protein levels. Thus, the antimicrobial mechanism of action affects macrophage inflammatory mediator production after stimulation with pneumococci.
authors.affiliation: Dept. of Pediatrics, University of Louisville, Louisville, KY 40202, USA. klorma01@gwise.louisville.edu
authors.forename: K L
authors.initials: KL
authors.lastname: Orman
authors.forename: B K
authors.initials: BK
authors.lastname: English
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002460:Cell Line; D002981:Clindamycin / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D010068:Oxacillin / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha; D002981:Clindamycin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D010068:Oxacillin