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.

<p>Arterial Stiffness Increases Over Time in Relation to Lung Diffusion Capacity: A Longitudinal Observation Study in COPD</p>

“…In addition, increased IL-6 and TNF-α could increase the expression of adhesion molecules on activated endothelial cells and facilitate the formation of atheromatous plaques. 38,39 In this study, hsCRP was independently associated with the evolution of arterial stiffness over time supporting the hypothesis that systemic inflammation could be an important determinant in the development of increased arterial stiffness and further cardiovascular risk in COPD patients. Although dyslipidaemia is a well-known, independent risk factor for cardiovascular disease, the relationship between serum lipids and arterial stiffness is still under debate.…”

Abnormal gene expression of proinflammatory cytokines and their receptors in the lymphocytes of patients with bipolar disorder

“…Whereas soluble cytokine receptors for IL‐1, IL‐6, and TNF‐α have been studied in the plasma of patients with BP and depressed patients, to our knowledge, the membrane‐bound receptors for these three proinflammatory cytokines have not been studied in either patients with BP or depressed patients. The soluble receptors for these cytokines, which have been studied in the plasma of patients with BP, may arise from the proteolytic cleavage of the extracellular domain of the original membrane‐bound receptors or by synthesis from alternatively spliced variants . They circulate at high concentrations in plasma, can induce cell activation, act as chaperones to extend cytokine bioavailability, or inhibit cytokine signaling .…”

“…The soluble receptors for these cytokines, which have been studied in the plasma of patients with BP, may arise from the proteolytic cleavage of the extracellular domain of the original membrane‐bound receptors or by synthesis from alternatively spliced variants . They circulate at high concentrations in plasma, can induce cell activation, act as chaperones to extend cytokine bioavailability, or inhibit cytokine signaling . However, the biological effects of the cytokines are mediated through their interactions with the membrane‐bound receptors through several signaling mechanisms, as mentioned above.…”

Diagnostic morphology: biophysical indicators for iron-driven inflammatory diseases

“…As their name implies, the various vascular diseases share a variety of properties, including raised levels of biochemical markers such as C-reactive protein, [23][24][25] fibrinogen 26 and leukocyte count, 27 as well as many small molecules characteristic of exposure to 'reactive oxygen species'. 28,29 Also raised are various cytokines such as tumor necrosis factor alpha (TNFa) and interleukin-6 (IL-6) that might serve as early indicators of vascular dysfunction, [30][31][32] and (most pertinently here) the iron storage protein ferritin. [33][34][35][36] The enzyme heme oxygenase-1 (HO-1) catalyzes the degradation of heme, and is the major source of free iron released from heme metabolism.…”