PMID- 10769273
OWN - NLM
STAT- MEDLINE
DCOM- 20000504
LR  - 20190623
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 101
IP  - 15
DP  - 2000 Apr 18
TI  - Hydroxymethylglutaryl coenzyme A reductase inhibitors modify the inflammatory 
      response of human macrophages and endothelial cells infected with Chlamydia 
      pneumoniae.
PG  - 1760-3
AB  - 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. 
      METHODS AND 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.
FAU - Kothe, H
AU  - Kothe H
AD  - Department of Internal Medicine II, Medical University of Lubeck, Germany.
FAU - Dalhoff, K
AU  - Dalhoff K
FAU - Rupp, J
AU  - Rupp J
FAU - Muller, A
AU  - Muller A
FAU - Kreuzer, J
AU  - Kreuzer J
FAU - Maass, M
AU  - Maass M
FAU - Katus, H A
AU  - Katus HA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Cytokines)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (NF-kappa B)
RN  - 0 (Pyridines)
RN  - 11062-77-4 (Superoxides)
RN  - AM91H2KS67 (cerivastatin)
SB  - IM
MH  - Adult
MH  - Arteriosclerosis/enzymology/pathology
MH  - Bronchitis/pathology
MH  - Cells, Cultured
MH  - Chlamydia Infections/*enzymology/*pathology
MH  - Chlamydophila pneumoniae
MH  - Chronic Disease
MH  - Cytokines/metabolism
MH  - Endothelium, Vascular/cytology/*drug effects
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology
MH  - Inflammation/enzymology/pathology
MH  - Macrophages, Alveolar/*drug effects/metabolism
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/metabolism
MH  - Pyridines/*pharmacology
MH  - Statistics, Nonparametric
MH  - Superoxides/metabolism
EDAT- 2000/04/19 00:00
MHDA- 2000/04/19 00:01
CRDT- 2000/04/19 00:00
PHST- 2000/04/19 00:00 [pubmed]
PHST- 2000/04/19 00:01 [medline]
PHST- 2000/04/19 00:00 [entrez]
AID - 10.1161/01.cir.101.15.1760 [doi]
PST - ppublish
SO  - Circulation. 2000 Apr 18;101(15):1760-3. doi: 10.1161/01.cir.101.15.1760.