Azithromycin inhibits interleukin-6 but not fibrinogen production in hepatocytes infected with cytomegalovirus and chlamydia pneumoniae
Abstract
Chlamydia pneumoniae and cytomegalovirus (CMV) have been associated with the development of atherosclerosis. Inflammatory stimuli initiate the biosynthesis of fibrinogen, interleukin (IL)-6 and plasminogen activator inhibitor (PAI)-1 in the liver. Chronic infection may perpetuate the inflammatory status. We hypothesized that infection of human hepatocytes with the intracellular pathogens C pneumoniae and CMV accelerates biosynthesis of fibrinogen, IL-6, and PAI-1 but that this biosynthesis can be reduced with the use of azithromycin. HepG2 human hepatocytes were infected with C pneumoniae and CMV in vitro in the presence of 0, 0.016, 0.125, or 1 microg/mL azithromycin. We measured IL-6, PAI-1, and fibrinogen after 24, 48, 72, and 96 hours. C pneumoniae-infected hepatocytes produce IL-6 (2667 +/- 309 pg/mL vs 137 +/- 120 pg/mL in uninfected cells after 96 hours. Incubation with 0.016 microg/mL azithromycin decreased IL-6 levels to a mean of 1516 +/- 402 pg/mL, and incubation with 0.125 and 1 microg/mL azithromycin decreased IL-6 to 871 +/- 364 and 752 +/- 403 pg/mL, respectively. C pneumoniae-induced IL-6 production was time- and dose-dependent. The interaction of C pneumoniae with azithromycin treatment was significant, indicat...Continue Reading
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