Acute-phase response of human hepatocytes after infection with Chlamydia pneumoniae and cytomegalovirus.

Abstract

There is increasing evidence that chronic inflammation plays a pivotal role in the development of atherosclerosis. Whether inflammation is the cause or consequence of vascular damage is unclear. Also, the source of inflammation is unknown, but may well be infection by Cytomegalovirus (CMV) or Chlamydia pneumoniae (C. pneumoniae). Infection of the liver by CMV or C. pneumoniae may induce a general inflammatory reaction contributing to accelerated atherogenesis. In this study we investigated the production of interleukin-6 (IL-6), fibrinogen and plasminogen activator inhibitor-1 (PAI-1) by hepatocytes after infection with CMV or C. pneumoniae. HepG2 cell monolayers were grown to confluence in 48-well tissue culture plates. Hepatocytes were infected with 50 microL or 100 microL of suspension of CMV (10(2.70) TCID50 mL(-1)) and C. pneumoniae (10(4.75) TCID50 mL(-1)). The medium of the inoculated cells was collected every 24 h, from day 1 to day 4, for determination of IL-6, PAI-1 and fibrinogen concentrations. Fibrinogen production was increased significantly in a dose-dependent manner after infection with CMV (50 microL: P=0.022 and 100 microL: P<0.001) and C. pneumoniae (P=0.012). Cytomegalovirus infection resulted in an increase of IL-6 production compared with uninfected cells (P=0.048). Cytomegalovirus and C. pneumoniae infection did not result in a significantly increase of PAI-1 production by hepatocytes. We conclude that in addition to direct vascular wall infection by C. pneumoniae and CMV, virus-related development of atherosclerosis might also be initiated by chronic liver infection and subsequent production of inflammatory and procoagulant mediators released in the circulation. This may be another pathophysiological link for the observed relation between infections and the development of atherosclerosis.