title: Supra-additive expression of interleukin-6, interleukin-8 and basic fibroblast growth factor in vascular smooth muscle cells following coinfection with Chlamydia pneumoniae and cytomegalovirus as a novel link between infection and atherosclerosis.
abstract: BACKGROUND
  Chlamydia pneumoniae and human cytomegalovirus (HCMV) may be involved in the pathogenesis of atherosclerosis. Prospective studies indicate an increased risk for cardiovascular events in patients with evidence of multiple infections.
  
  
  OBJECTIVE
  To determine whether there is a synergistic effect of coinfection with C pneumoniae and HCMV on expression of selected growth factors and cytokines.
  
  
  METHODS
  The production of interleukin (IL)-6, IL-8, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and 'regulated on activation normal T-cell expressed and secreted' (RANTES) was measured in coinfected aortic smooth muscle cells (AoSMC).
  
  
  RESULTS
  Using reverse transcription polymerase chain reaction and immunoassays, it was demonstrated that the expression of IL-6, IL-8, RANTES and bFGF was stimulated in a dose- and time-dependent fashion in C pneumoniae and also in HCMV-infected cultures. In contrast, the expression of PDGF-AA was only stimulated following HCMV infection. Coinfection with C pneumoniae and HCMV resulted in a supra-additive stimulation of IL-6 (30% increased expression, P≤0.05) at 48 h, IL-8 (137% increased expression, P≤0.001) at 24 h and bFGF (209% increased expression, P≤0.01) at 48 h following infection.
  
  
  CONCLUSIONS
  The findings of the present study show that C pneumoniae and HCMV are able to act in synergy in coinfected AoSMC. The supra-additive induction of AoSMC growth factors and cytokines indicates a novel molecular link between infection and vascular disease development.
authors.affiliation: Department of Internal Medicine/Cardiology;
authors.forename: Dirk
authors.initials: D
authors.lastname: Prochnau
authors.forename: Eberhard
authors.initials: E
authors.lastname: Straube
authors.forename: Hans-Reiner
authors.initials: HR
authors.lastname: Figulla
authors.forename: Jürgen
authors.initials: J
authors.lastname: Rödel
keywords: Atherosclerosis; Chlamydia pneumoniae; Coinfection; Cytomegalovirus; Smooth muscle cells