Modulation of immune activation and lipoproteins in chronic heart failure

ABSTRACT

Heart failure is a major problem of public health associated with poor outcome in the advanced stages, thus justifying its prevention based on the prevention and treatment of its principle etiological factors. In chronic heart failure mesenteric venous congestion leads to increased bowel permeability, bacterial translocation and thereby endotoxin release. The increased endotoxine challenge is hypothesized to cause immune activation, which might have an important role in the progression of heart failure. This study is designed to examine the degree of immune activation, to study the degree of endotoxin, interaction and to evaluate the beneficial immune regulatory effects of high density lipoprotein, [HDL] as an endotoxin, binding protein in CHF. We studied thirty five patients with CHF [Age 50+9 Years NYHA 2.7 +/- 0. 4, LVEF 28.0 +/- 6 all mean +/- SEM and eight healthy control subjects matched for age and sex. Serum levels of cholesterol, HDL-C, LDL-C, soluble tumor necrosis factor-alpha [sTNE-alpha], soluble tumor necrosis factor reteptor-l [sTNFl]., sCDI4, kidney function test, and liver function test were assessed. Patients with CHF had increased concentration of sTNF-Rl [P=0.005], TNF- alpha <0.05. whereas HDL levels were decreased [P=0.007]. sCDl4 [indicative of endotoxine cell interaction] was significantly increased, and correlated positively with TNF-alpha [r=0.68, P<0.001] and inversely with MDL. TNF-alpha as a measure of immune activation was inversely correlated with HDL [r=0.36, P=0.045]. From the present study we could concluded that in CHF patients increased concentrations of sCDI4 are related to lower HDL levels and increased concentration of TNF-alpha. This may support the role of HDL in the modulation of immune activation and cytokine and cytokine release in CHF