Hydroxymethylglutaryl coenzyme A reductase inhibitors modify the inflammatory response of human macrophages and endothelial cells infected with Chlamydia pneumoniae

Background-In patients with atherosclerosis, hepatic hydroxymethylglutaryl coenzyme A reductase (CSE) inhibitors may reduce the activation of inflamma tion. Because Chlamydia pneumoniae infection has been linked to coronary ar tery disease through the induction of plaque inflammation, we investigated whether cerivastatin affects the infection rate of human macrophages and en dothelial cells (ECs) and their proinflammatory activation after chlamydial infection. Methods and Results-Macrophages were collected from the alveolar compartmen t of 6 volunteers and 10 patients with chronic bronchitis. ECs were obtaine d from 10 umbilical cords. The C. pneumoniae strain CWL was incubated with macrophages or ECs in the presence and absence of the CSE inhibitor cerivas tatin. The infection rate was determined by immunofluorescence microscopy. The release of monocyte chemoattractant protein-1 (MCP-1), interleukin-8 (I L-8), and tumor necrosis factor (TNF)-alpha was quantified by ELISA. The re lease of oxygen radicals was determined by ferricytochrome assay. Infection rates were tendentially lower after the the incubation 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 fr om volunteers increased. Coincubation with cerivastatin resulted in signifi cantly lower MCP-1 and IL-8 production, whereas the release of TNF-alpha re mained unaffected. Similar effects regarding chemokine release were observe d 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. pneumonia e infection.