Circulating Interleukin-6 and Interleukin-6 Receptors in Patients with Acute and Recent Myocardial Infarction

Abstract

Interleukin-6 (IL-6), a proinflammatory cytokine, plays a key role in the pathogenesis of coronary artery disease (CAD). We investigated circulating IL-6 and its receptors in patients with CAD. We evaluated 39 Japanese patients with CAD (30 males and 9 females aged 36–79 years), measuring their plasma levels of IL-6 and IL-6 receptors α and β (IL-6Rα, IL-6Rβ). Circulating levels of IL-6, IL-6Rα and IL-6Rβ were measured by an enzyme-linked immunosorbent assay. Blood was sampled immediately after admission and again after 1, 2, 3, 6 and 9 h, then every 12 h for 5 days. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were measured on day 3 after symptom onset. Plasma levels of IL-6 and IL-6Rs were significantly increased in 28 patients with acute myocardial infarction (AMI) compared with 15 normal controls. However, neither IL-6 nor IL-6Rs showed an increase in 6 patients with angina pectoris. We observed two peaks for circulating IL-6 in AMI, the first of which showed a significant correlation with ANP as well as BNP. These results may help to explain why the amount of IL-6 produced is closely related to the severity of myocardial dysfunction in patients with CAD.

α1-Adrenergic Receptor Stimulates Interleukin-6 Expression and Secretion through Both mRNA Stability and Transcriptional Regulation: Involvement of p38 Mitogen-Activated Protein Kinase and Nuclear Factor-κB

“…Evidence indicates that IL-6 is involved in cardiovascular diseases, such as cardiac hypertrophy, myocardial infarction, and heart failure (Hirota et al, 1995;Kanda et al, 2000). Overexpression of signal transducer and activator of transcription 3, a major component in IL-6 signaling, was sufficient to induce hypertrophy of CMs (Kunisada et al, 1998).…”

Genetic Profiling of α1-Adrenergic Receptor Subtypes by Oligonucleotide Microarrays: Coupling to Interleukin-6 Secretion but Differences in STAT3 Phosphorylation and gp-130

“…This effect of ␣ 1 -ARs may be relevant during the pathogenesis of congestive heart failure, because plasma concentrations of the sympathetic neurotransmitter norepinephrine are elevated during the onset of heart failure. In addition to increased cardiac sympathetic drive, circulating levels of the proinflammatory cytokine IL-6 (and IL-6 family members LIF and cardiotrophin-1) are also elevated in patients with heart failure (Kanda et al, 2000;Eiken et al, 2001;Ng et al, 2002). A role for IL-6 in the development of heart failure has been proposed based upon evidence that mice overexpressing IL-6 or its receptor develop ventricular hypertrophy (Hirota et al, 1995), whereas IL-6 receptor or gp-130 knockout mice develop thin ventricular walls (Taga et al, 1996) or a massive apoptosis before the onset of heart failure (Hirota et al, 1999).…”

Novel α1-Adrenergic Receptor Signaling Pathways: Secreted Factors and Interactions with the Extracellular Matrix

“…IL-6 is a secreted proinflammatory cytokine that plays key roles in cell growth, differentiation, inflammation, and in the pathogenesis of many diseases, such as cardiac hypertrophy and coronary artery disease (Kanda et al, 2000). In addition to our previous study, which demonstrated ␣ 1 -AR subtypedependent effects on IL-6/gp130/stat3 signaling (GonzalezCabrera et al, 2003), the up-regulation of IL-6 mRNA and protein secretion was also reported in astrocytes and hepatocytes after ␣ 1 -AR activation (Norris and Benveniste, 1993;Jung et al, 2000).…”