Paraventricular Nucleus Interleukin‐6 Receptor Expression in Heart Failure

Abstract

Heart failure (HF) increases sympathetic nerve discharge (SND) and plasma interleukin 6 (IL-6) levels, which directly correlate with disease severity. Previous research has shown increased mRNA levels of the interleukin-6 receptor (IL-6R) within the paraventricular nucleus (PVN), a forebrain nucleus that integrates autonomic and endocrine signals. The central actions of the immunoregulatory cytokine IL-6 are highly dependent upon the cytokine binding the translated form of the IL-6R. The current study tested the hypothesis that PVN expression of the IL-6R complex is enhanced in HF compared to sham-operated controls. Rats underwent a left-coronary artery ligation (n=15) or sham operation (n=8). Eight weeks after surgery hemodynamic measurements were taken, blood samples collected, brain tissue harvested, and protein analysis performed. Brains were cut in the coronal plane and bilateral punches of PVN and non-PVN sites were taken. Left ventricular end-diastolic pressure (LVEDP) readings were used to divide HF rats into severe (LVEDP ≥ 20 mm Hg) and moderate (LVEDP <20 mm Hg) HF groups. Consistent with previous findings, plasma levels of IL-6 showed a direct correlation with severity of HF. PVN protein expression of IL-6R increased with the severity of HF whereas expression of the beta subunit protein, gp130, was independent of HF severity. These preliminary results suggest that the central expression of the IL-6R is upregulated in HF rats. This upregulation provides a possible path by which IL-6 may alter SND regulation during HF. Supported by NHLBI HL 69755-04, HL 065346-04, and AHA 0520105Z