Enhanced gene expression of chemokines and their corresponding receptors in mononuclear blood cells in chronic heart failure - Modulatory effect of intravenous immunoglobulin

Objectives We sought to study the gene expression of chemokines and their c orresponding receptors in mononuclear blood cells (MNCs) from patients with chronic heart failure (CHF), both of which were cross-sectional and longit udinal studies during therapy with intravenous immunoglobulin (IVIg). Background We have recently demonstrated that IVIg improves left ventricula r ejection fraction (LVEF) in patients with CHF. Based on the potential pat hogenic role of chemokines in CHF, we hypothrsized that the beneficial effe ct of IVIg may be related to a modularory effect on the expression of chemo kines and their receptors in MNCs. Methods We examined: 1) the gene expression of C, CC and CXC chemokines and their receptors in MNCs from 20 patients with CHF and 10 healthy blood don ors; and 2) the expression of these genes in MNCs from 20 patients with CHF randomized in a double-blind fashion to therapy with IVlg or placebo for 2 6 weeks. Results Our main findings in CHF were: 1) markedly raised gene expression o f macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta and interleukin (IL)-8; 2) enhanced gene expression of their corresponding receptors; 3) m odulation in a normal direction of this abnormal chemokine and chemokine re ceptor gene expression during IVIg, but not during placebo therapy; 4) down -regulation of MIP-1 alpha, MIP-1 beta and IL-8 during IVlg at the protein level in plasma; and 5) a correlation between down-regulation of MIP-1 alph a gene expression and improved LVEF during IVlg therapy. Conclusions Our results further support a pathogenic role for chemokines in CHF and suggest that IVlg may represent a novel therapeutic approach, with the potential to improve LVEF in patients with CHF, possibly by modulatory effects on the chemokine network. (J Am Coll Cardiol 2001;38:187-93) (C) 2 001 by the American College of Cardiology.