Pro-inflammatory cytokines and their receptors in chronic heart failure: do they really matter?

The pathophysiological insights into the chronic heart failure (CHF) syndrome and, consequently, the management of patients with CHF have dramatically changed over the past few decades. Antagonists of the activated neurohormonal pathways are now a mainstay in the therapeutic arsenal. It seems, however, that a neurohormonal ceiling might have been reached. Other humoral mal-adaptations have recently gained importance. One of them is the presence of a low-grade inflammatory status characterising patients with moderate to severe CHF. The presence, both at tissue level and in the circulation, of increased levels of pro-inflammatory cytokines suggests that immune activation might be a relevant mechanism contributing to cardiac as well as peripheral manifestations of the disease. Whereas targeted anti-cytokine treatment has proven unsuccessful in the CHF population, the concept of immune modulation is still intensively studied.