New insights into the pathophysiological role for cytokines in heart failure

Time for primary review 29 days. The syndrome of heart failure may be produced by a variety of disease states. These include dilated cardiomyopathy, mechanically overloaded hypertrophy or ischemic heart disease. We developed experimental models of these cardiac diseases. In the murine model of myocarditis, inflammatory cytokines were induced rapidly in the myocardium and continued to express during the chronic stage when the heart assumed the typical pattern of dilated cardiomyopathy in the absence of inflammatory processes. In the pressure overloaded ventricle, the myocardium first developed adaptive hypertrophy but in the later stage this pattern of hypertrophy underwent a transition to heart failure. Cytokines appeared to play a significant role in this process by accelerating myocyte growth and down-modulating cardiac function. In the ischemic heart, the non-ischemic myocardium developed hypertrophy associated with the progression of scarring in the ischemic area. This remodelling process initially exerts an important compensatory mechanism for ventricular function but later results in the development of heart failure. During this stage of healing from acute ischemic insult, inflammatory cytokines were upregulated continuously in the non-ischemic myocardium. Thus, we postulated that some aspects of heart failure may be mediated by non-lethal alteration of cardiac function and structural changes of the ventricle induced by cytokines. In this connection, many drugs used routinely in clinical practice have been proved to have anticytokine effects. Immunomodulating or anticytokine therapy could pave a new road in the management of heart failure. There is a growing body of evidence that immunologic responses mediated by cytokines may play an important pathogenic role in the development of heart failure. A number of clinical studies have demonstrated that patients with congestive heart failure (CHF) express excessive levels of cytokines in plasma 1–4. Cytokines are soluble peptides which mediate cell-to-cell interactions via specific cell surface receptors and … * Corresponding author. Tel.: +81-75-751-3185; Fax:+81-75-752-0856