title: Roles of interleukin-6 and macrophage inflammatory protein-2 in pneumolysin-induced lung inflammation in mice.
abstract: Pneumolysin (PLY), a toxin synthesized by Streptococcus pneumoniae, is an important virulence factor in pneumococcal disease. This study evaluated the effects of PLY in lungs of mice. Intranasal inoculation with PLY was associated with a dose-dependent influx of polymorphonuclear leukocytes (PMNL) in bronchoalveolar lavage fluid (BALF) and increased concentrations of interleukin (IL)-6, macrophage inflammatory protein (MIP)-2, and KC in BALF. PLY mutants with either reduced cytolytic activity or reduced cytolytic and complement-activating activities were less potent in inducing PMNL recruitment to the lung (P<.05), which suggests that PLY cytolytic activity is very important for the inflammatory response. IL-6 and MIP-2 also played a role in PLY-induced PMNL recruitment; this response was partially diminished in IL-6 gene-deficient mice and in mice treated with anti-MIP-2 antiserum. PLY may play an important role in the induction of an inflammatory response in the pulmonary compartment in the early phase of pneumococcal pneumonia.
authors.affiliation: Department of Experimental Internal Medicine, Tropical Medicine, and AIDS, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands. a.w.rijneveld@amc.uva.nl
authors.forename: Anita W
authors.initials: AW
authors.lastname: Rijneveld
authors.forename: Germie P
authors.initials: GP
authors.lastname: van den Dobbelsteen
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Theodore J
authors.initials: TJ
authors.lastname: Standiford
authors.forename: Peter
authors.initials: P
authors.lastname: Speelman
authors.forename: Loek
authors.initials: L
authors.lastname: van Alphen
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D001426:Bacterial Proteins; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis*; D002634:Chemotaxis, Leukocyte; D005260:Female; D015850:Interleukin-6 / Q000096:biosynthesis*; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009504:Neutrophils / Q000276:immunology; D011014:Pneumonia / Q000276:immunology*; D013301:Streptolysins / Q000009:adverse effects* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D015850:Interleukin-6; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae