title: Hydroxymethylglutaryl coenzyme A reductase inhibitors modify the inflammatory response of human macrophages and endothelial cells infected with Chlamydia pneumoniae.
abstract: BACKGROUND
  In patients with atherosclerosis, hepatic hydroxymethylglutaryl coenzyme A reductase (CSE) inhibitors may reduce the activation of inflammation. Because Chlamydia pneumoniae infection has been linked to coronary artery disease through the induction of plaque inflammation, we investigated whether cerivastatin affects the infection rate of human macrophages and endothelial cells (ECs) and their proinflammatory activation after chlamydial infection.
  
  
  RESULTS
  Macrophages were collected from the alveolar compartment of 6 volunteers and 10 patients with chronic bronchitis. ECs were obtained from 10 umbilical cords. The C. pneumoniae strain CWL was incubated with macrophages or ECs in the presence and absence of the CSE inhibitor cerivastatin. The infection rate was determined by immunofluorescence microscopy. The release of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (IL-8), and tumor necrosis factor (TNF)-alpha was quantified by ELISA. The release of oxygen radicals was determined by ferricytochrome assay. Infection rates were tendentially lower after the preincubation of macrophages with CSE inhibitors (17.2% versus 9. 3% and 18.2% versus 10.4%, respectively; P=NS). The secretion of MCP-1, IL-8, and TNF-alpha by infected macrophages from volunteers increased. Coincubation with cerivastatin resulted in significantly lower MCP-1 and IL-8 production, whereas the release of TNF-alpha remained unaffected. Similar effects regarding chemokine release were observed in ECs.
  
  
  CONCLUSIONS
  CSE inhibitors modify the inflammatory response of human immune cells to C. pneumoniae. This finding could be relevant for the therapeutic potential of CSE statins in patients with atherosclerosis and C. pneumoniae infection.
authors.affiliation: Department of Internal Medicine II, Medical University of Lübeck, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kothe
authors.forename: K
authors.initials: K
authors.lastname: Dalhoff
authors.forename: J
authors.initials: J
authors.lastname: Rupp
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.forename: J
authors.initials: J
authors.lastname: Kreuzer
authors.forename: M
authors.initials: M
authors.lastname: Maass
authors.forename: H A
authors.initials: HA
authors.lastname: Katus
mesh_terms: D000328:Adult; D001161:Arteriosclerosis / Q000201:enzymology / Q000473:pathology; D001991:Bronchitis / Q000473:pathology; D002478:Cells, Cultured; D002690:Chlamydia Infections / Q000201:enzymology* / Q000473:pathology*; D016993:Chlamydophila pneumoniae; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007249:Inflammation / Q000201:enzymology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D018709:Statistics, Nonparametric; D013481:Superoxides / Q000378:metabolism
chemical_list: D016207:Cytokines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016328:NF-kappa B; D011725:Pyridines; D013481:Superoxides; C086276:cerivastatin