Activation of immune and inflammatory systems in chronic heart failure: novel therapeutic approaches.

Despite extensive research and novel treatments, chronic heart failure (CHF) remains a cause of high morbidity and mortality. Mounting evidence suggested that immune activation and inflammation play critical roles in the pathogenesis of CHF. In this review, we examine the current evidence regarding this contemporary pathophysiological mechanism, and evaluate the effects of conventional and novel cardiovascular drugs, such as calcium sensitisers and statins, on the immune and inflammatory mediator's network. Although therapies, which specifically antagonise tumour necrosis factor-alpha have not demonstrated considerable benefit in patients with CHF, there is an increasing evidence to suggest greater value from non-specific anti-inflammatory approaches, including: pentoxifylline, intravenous immunoglobulin, immune modulation therapy, growth hormones, physical training and nutrition regulation. Several innovative therapeutic targets, such as peroxisome proliferator-activated receptor gamma activators, Rho-kinase, p38 mitogen-activated protein kinase, nuclear transcription factor NF-kappaB, recovering or augmenting parasympathetic tone, cardiac resynchronisation therapy, macrophage inhibitors and chemokine receptor antagonists, are briefly discussed in this review. While we have recently demonstrated the potential merits of combining low-dose methotrexate with conventional therapy, through extensively modulating the activated immune and inflammatory mediator's network, there is a need for further rigorous research of this complex network, especially involving current promising therapies which modulate this system. Such evidence has the potential to revolutionise changes for the management of this disorder. Based on the 'heterogeneity' of immune activation and inflammation among different CHF populations, an 'optimised combination treatment' may offer exciting benefits for individual therapy in the future.