Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure

Background-Congestive heart failure (CHF) is characterized by enhanced immu ne activation, and immune-mediated mechanisms may play a pathogenic role in this disorder. Based on the immunomodulatory effects of intravenous immuno globulin (IVIG), we hypothesized that IVIG could downregulate inflammatory responses in CHF patients and have potential beneficial effects on the left ventricular ejection fraction (LVEF). Methods and Results-Forty patients with chronic symptomatic CHF and LVEF of <40%, stratified according to cause (ie, ischemic and idiopathic dilated c ardiomyopathy), were randomized in a double blind fashion to receive therap y with IVIG or placebo for a total period of 26 weeks. Our main findings we re that (1) IVIG, but not placebo, induced a marked rise in plasma levels o f the anti-inflammatory mediators interleukin (IL)-10, IL-1 receptor antago nist, and soluble tumor necrosis factor receptors, (2) significantly correl ated with these anti-inflammatory effects, IVIG, but not placebo, induced a significant increase in LVEF from 26+/-2% to 31+/-3% (P<0.01), and this wa s found independent of the cause of heart failure; and (3) N-terminal pro-a trial natriuretic peptide decreased significantly after induction therapy a nd : continued to decrease toward the end of study during IVIG therapy (P<0 .001) but remained unchanged during placebo. Conclusions-We demonstrated an IVIG-induced change in the balance between i nflammatory and anti-inflammatory cytokines that favored an anti-inflammato ry net effect in CHF. This effect was significantly correlated with an impr ovement in LVEF, suggesting a potential for immunomodulating therapy in add ition to optimal conventional cardiovascular treatment regimens in CHF pati ents.