Enhanced interleukin-1 activity contributes to exercise intolerance in patients with systolic heart failure.

Benjamin W Van Tassell
Ross A Arena
Stefano Toldo
Eleonora Mezzaroma
Tania Azam
Ignacio M Seropian
Keyur Shah
Justin Canada
Norbert F Voelkel
Charles A Dinarello
Antonio Abbate

Open link

DOI

10.1371/journal.pone.0033438

Publisher

Public Library of Science (PLoS)

Journal

issn:1932-6203

Abstract

Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects.We developed a model of IL-1β-induced left ventricular (LV) dysfunction in healthy mice that exhibited a 32% reduction in LV fractional shortening (P<0.001) and a 76% reduction in isoproterenol response (P<0.01) at 4 hours following a single dose of IL-1β 3 mcg/kg. This phenotype was reproducible in mice injected with plasma from HF patients and fully prevent...