Nuclear factor-kappaB activity in peripheral blood mononuclear cells in cachectic and non-cachectic patients with chronic heart failure

Abstract

Background Inflammatory immune mechanisms are involved in the pathogenesis and progression of chronic heart failure (CHF), and also promote the development of generalised body wasting seen in this syndrome. We examined the activity of nuclear factor kappa-B (NF-κB), the major mediator of immune response, in peripheral blood mononuclear cells (PBMC) isolated from cachectic and non-cachectic patients with CHF. Methods Using electromobility shift assay, NF-κB activity was assessed in nuclear fractions of PBMC isolated from 43 patients with systolic CHF (88% men, age: 64 years [median], left ventricular ejection fraction [LVEF]: 30%, ischaemic CHF aetiology: 79%, NYHA class [I/II/III/IV]: 2/21/19/1, 10 patients with cardiac cachexia) and 12 healthy adult subjects. Results As compared to healthy controls, NF-κB activity in PBMC was increased in patients with CHF ( P < 0.05), in particular in those with severe CHF (NYHA class III–IV) ( P < 0.05). NF-κB activity in PBMC in CHF patients was not related either to age, sex, CHF aetiology, LVEF, or any clinical parameters reflecting disease severity (haemoglobin, LDL cholesterol, sodium and creatinine levels) (all P > 0.1). Regardless of the severity of CHF expressed as NYHA class, patients with cardiac cachexia demonstrated significantly reduced NF-κB activity in PBMC as compared to both non-cachectic CHF patients ( P < 0.001) and healthy controls ( P < 0.05). Conclusion The activity of NF-κB system in peripheral immune cells is augmented in patients with advanced CHF, whereas it is diminished in those with cardiac cachexia. The significance of derangements within NF-κB system in PBMC for immune phenomena seen in cachectic and non-cachectic CHF patients remains further studies.