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.