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Inflammatory cytokines in heart failure: roles in aetiology and utility as biomarkers

Leonardo Tamariz, Joshua M. Hare
DOI: http://dx.doi.org/10.1093/eurheartj/ehq014 768-770 First published online: 19 February 2010

This editorial refers to ‘Relationship of interleukin-6 with regional and global left-ventricular function in asymptomatic individuals without clinical cardiovascular disease: insights from the Multi-Ethnic Study of Atherosclerosis’, by A.T. Yan et al. on page 875

The pathogenesis of left ventricular (LV) failure and cardiomyopathy, especially in the absence of ischaemic injury, remains incompletely understood. Among the key pathways implicated in the evolution of myocardial failure are neurohormonal activation,1 oxidative stress/nitroso–redox imbalance,2 and immune activation.3 Support for immune activation in heart failure comes from studies showing increased levels of inflammatory cytokines in patients with heart failure and increased expression of immunological antigens within the heart.1 With regard to the former, levels of inflammatory cytokines correlate with both severity of heart failure and the development of heart failure in asymptomatic patients, and as such these mediators may have both pathophysiological importance and utility as clinically predictive biomarkers.

A key issue arising from these associations is whether the cytokines are causally or non-causally correlated with disease pathophysiology. This is addressed by studies in which a cytokine is experimentally overexpressed.3 Indeed, in the case of tumour necrosis factor-α (TNF-α), classically shown to be associated with heart failure severity, it is shown that direct animal injections mimicked endotoxin-induced septic shock.4 Furthermore, injections of antibodies against TNF-α attenuated the haemodynamic collapse seen in those animals.5 Other studies in rats have shown that circulating concentrations of TNF-α similar to those seen in patients with heart failure are sufficient to produce persistent negative inotropic effects that are detectable at the level of the cardiac myocyte and are completely reversible after TNF-α is stopped.6 Similar findings have been reported in cardiac restricted transgenic overexpression of TNF-α; however, recent experimental data suggest that only ablation of the gene for TNF receptor 1 …

*Corresponding author. Tel: +1 305 243 5579, Fax: +1 305 243 5584, Email: jhare{at}med.miami.edu