(Circulation. 2000;101:1760.)
© 2000 American Heart Association, Inc.
Brief Rapid Communications |
Hydroxymethylglutaryl Coenzyme A Reductase Inhibitors Modify the Inflammatory Response of Human Macrophages and Endothelial Cells Infected With Chlamydia pneumoniae
From the Department of Internal Medicine II (H.K., K.D., J.R., H.A.K.), the Institute of Microbiology (M.M.), the Department of Rheumatology (A.M.), Medical University of Lübeck; and the Department for Internal Medicine III (J.K.), University of Heidelberg, Germany.
Correspondence to K. Dalhoff, Med Klinik II, Medizinische Universität, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
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)-
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- by infected macrophages
from volunteers increased. Coincubation with cerivastatin resulted in
significantly lower MCP-1 and IL-8 production, whereas the
release of TNF- 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.
Key Words: inflammation • endothelium • atherosclerosis • infection
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