title: C-reactive protein-induced production of interleukin-18 in human endothelial cells: a mechanism of orchestrating cytokine cascade in acute coronary syndrome.
abstract: The circulating interleukin (IL)-18 level is a strong predictor of death from cardiovascular causes in patients with coronary artery disease. However, the mechanisms of IL-18 in orchestrating the cytokine cascade and the accelerator of IL-18 production in atherosclerosis are still unknown. In the present study, we measured the serum concentration of IL-18 and other markers of inflammation in 35 patients with acute coronary syndrome. To determine the mechanism of accelerating IL-18 production, we examined the release of IL-18 in human endothelial cells using human recombinant (hr) C-reactive protein (CRP) as a stimulator of IL-18. Furthermore, we investigated the inhibitory effects of hr IL-10 on IL-18 production by hr CRP in human endothelial cells. Circulating levels of IL-18 were significantly higher in patients with acute myocardial infarction than in patients with unstable angina. Incubation with hr CRP, which was equivalent to the serum concentration in patients with acute coronary syndrome, induced IL-18 release. Treatment with hr IL-10 inhibited IL-18 release in the cells stimulated with hr CRP. The serum level of IL-18 was identified as a marker of severity in acute coronary syndrome. Our findings reveal the possibility that circulating CRP by itself could cause a deterioration of the inflammatory cascade in endothelial cells associated with the upregulation of IL-18. This suggests that CRP may contribute to the mechanism of coronary artery disease in addition to being an incidental product of various types of systemic inflammation.
authors.affiliation: Department of Internal Medicine and Cardiology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan. myamaoka-circ@umin.ac.jp
authors.forename: Minako
authors.initials: M
authors.lastname: Yamaoka-Tojo
authors.forename: Taiki
authors.initials: T
authors.lastname: Tojo
authors.forename: Takashi
authors.initials: T
authors.lastname: Masuda
authors.forename: Yoji
authors.initials: Y
authors.lastname: Machida
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kitano
authors.forename: Toshirou
authors.initials: T
authors.lastname: Kurosawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood*; D042783:Endothelial Cells / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood
chemical_list: D015415:Biomarkers; D020382:Interleukin-18; D020097:Natriuretic Peptide, Brain; D016753:Interleukin-10; D002097:C-Reactive Protein