title: Acellular components of Chlamydia pneumoniae stimulate cytokine production in human blood mononuclear cells.
abstract: Accumulating evidence suggest that infection with Chlamydia pneumoniae is associated with atherosclerosis, but the mechanisms involved remain unclear. Inflammation is important in the initial phase of atherogenesis, and cytokines are important in the initiation and progression of inflammation. The aim of this study was to assess the capacity of acellular components of C. pneumoniae to stimulate the production of pro-inflammatory cytokines and chemokines. Peripheral blood mononuclear cells were stimulated in vitro with sonicated C. pneumoniae. Significant amounts of TNF-alpha, IL-1, IL-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) were produced. Inhibition of endotoxin using polymyxin B revealed that chlamydial endotoxin plays a minor role in the cytokine induction. Neutralization of TNF by TNF-binding protein and blockade of IL-1 receptors by IL-1 receptor antagonist revealed that TNF, IL-1 and IL-6 production was independent from each other, whereas IL-8 synthesis was strongly dependent on endogenous TNF and IL-1. In contrast, synthesis of MCP-1 and MIP-1alpha was dependent on endogenous TNF, but not IL-1. In conclusion, acellular components of C. pneumoniae are a potent stimulus for cytokine production, and this mechanism may have an important role in the inflammatory aspects of atherogenesis.
authors.affiliation: Department of Medicine, University Hospital Nijmegen, Nijmegen, The Netherlands. M.Netea@aig.azn.nl
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.forename: C H
authors.initials: CH
authors.lastname: Selzman
authors.forename: B J
authors.initials: BJ
authors.lastname: Kullberg
authors.forename: J M
authors.initials: JM
authors.lastname: Galama
authors.forename: A
authors.initials: A
authors.lastname: Weinberg
authors.forename: A F
authors.initials: AF
authors.lastname: Stalenhoef
authors.forename: J W
authors.initials: JW
authors.lastname: Van der Meer
authors.forename: C A
authors.initials: CA
authors.lastname: Dinarello
mesh_terms: D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000276:immunology*; D016993:Chlamydophila pneumoniae / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000382:microbiology
chemical_list: D016207:Cytokines