title: Soluble TNF and IL-6 receptors: indicators of vascular health in women without cardiovascular disease.
abstract: Cytokine receptor subunits are released from cells in a regulated manner and circulate in soluble forms at concentrations that are orders of magnitude greater than the concentrations of the cytokines themselves. The purpose of this study was to determine if the circulating concentrations of soluble receptor subunits for interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα) and interleukin-6 (IL-6) might serve as early indicators of vascular dysfunction independent of the traditional cardiovascular disease (CVD) risk factors in women. Healthy women, aged 20-50 years (n = 36), were assessed for circulating concentrations of the cytokines IL-1β, IL-6 and TNFα and the soluble cytokine receptor subunits interleukin-1 receptor type I (sIL-1RI), sIL-1RII, sIL-6Rα, glycoprotein 130 (s-gp130), soluble TNF receptor type 1 (sTNFR1), and sTNFR2, along with traditional CVD risk factors. Cytokine receptor subunit expression on mononuclear cells and the release of these subunits in vitro were also determined. Brachial artery flow-mediated dilation (FMD), carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cfPWV) were assessed by ultrasonography and Doppler probes. Circulating sIL-6Rα correlated negatively with FMD (r = -0.56, p = 0.007) independent of age and other CVD risk factors. Circulating sTNFR1 correlated positively with cfPWV (r = 0.60, p = 0.002). TNFR1 receptor expression on monocytes correlated positively with cIMT (r = 0.51, p = 0.004). Plasma concentrations of IL-1β, IL-6 and TNFα were not significantly associated with FMD, cIMT or cfPWV. These data suggest that the receptors for IL-6 and TNFα, rather than the cytokines themselves, may be better indicators of early vascular changes that are associated with CVD.
authors.affiliation: College of Allied Health Sciences, Georgia Regents University, Augusta, GA, USA.
authors.forename: Miriam
authors.initials: M
authors.lastname: Cortez-Cooper
authors.forename: Eric
authors.initials: E
authors.lastname: Meaders
authors.forename: Judith
authors.initials: J
authors.lastname: Stallings
authors.forename: Sara
authors.initials: S
authors.lastname: Haddow
authors.forename: Barbara
authors.initials: B
authors.lastname: Kraj
authors.forename: Gloria
authors.initials: G
authors.lastname: Sloan
authors.forename: Kevin K
authors.initials: KK
authors.lastname: McCully
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Cannon
mesh_terms: D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D059168:Carotid Intima-Media Thickness; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D063177:Pulse Wave Analysis; D018121:Receptors, Cytokine / Q000097:blood; D017472:Receptors, Interleukin-1 / Q000097:blood; D019947:Receptors, Interleukin-6 / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood*; D012307:Risk Factors; D012995:Solubility; D059289:Vascular Stiffness; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018121:Receptors, Cytokine; D017472:Receptors, Interleukin-1; D019947:Receptors, Interleukin-6; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II
keywords: atherosclerosis; cytokines; endothelium; monocytes; vascular