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The European Society of Cardiology

Immune activation in severe heart failure

Does etiology play a role?

Laura Agnolettia, Salvatore Curellob, Fabio Malacarnec, Paolo Airòc, Anna Cargnonia, Marco Valgimiglid and Roberto Ferrarid,*,1

a Cardiovascular Pathophysiology Research Center, S. Maugeri Foundation IRCCS, Gussago, Brescia, Italy
b Chair of Cardiology, Spedali Civili, Brescia, Italy
c Immunology Department, Spedali Civili, Brescia, Italy
d Chair of Cardiology, Cardiovascular Pathophysiology Research Center, S. Maugeri Foundation IRCCS and University of Ferrara, Via Pinidolo 23, 25064 Gussago, Brescia, Italy

* Correspondence: Tel.: +39 30 252 8391; fax: +39 30 252 2362 (E-mail: fri{at}dns.unife.it).

Abstract

AIM: Immune activation in severe congestive heart failure (CHF) due to idiopathic conditions is a well-known phenomenon. The question remains: is it confined to a specific aetiology or is a disease-dependent derangement? We investigated immune alterations in ischaemic compared to idiopathic patients with CHF and healthy subjects.

METHODS AND RESULTS: We evaluated alterations of immune activation studying both in vivo and in vitro parameters. In both idiopathic and ischaemic CHF patients: (a) lymphocyte count was reduced (P<0.01); (b) lymphocyte subsets were altered (CD4/CD8 ratio increased vs. controls: 2.53±0.8 and 3.3±2.1% in idiopathic and ischaemic patients, vs. 1.8±0.6% in controls; P<0.01); (c) lymphocytes from patients underwent a higher apoptosis (27.1±4.3% in idiopathic CHF and 25.4±3.5% in ischaemic CHF vs. 4.5±1.4%; P<0.0001); (d) TNF-α production from lymphocytes and monocytes of patients was higher than controls. A positive correlation was observed between TNF-α from monocytes of patients and the relevant serum levels (r=0.58; P<0.01); (e) conditioned media of lymphocytes and monocytes from patients significantly increased rate of endothelial apoptosis.

CONCLUSIONS: In severe CHF, irrespectively from aetiology, significant activation of immune system occurs: several pro-inflammatory cytokines and soluble factors are spontaneously released in serum, possibly contributing to disease progression, as they induce apoptosis.

Keywords Congestive heart failure; Immune system activation; TNF-α


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