The role of TNF in cardiovascular disease

There is increasing evidence that cytokines in general and tumour necrosis factor (TNF) in particular play an important role in cardiovascular disease. This is not surprising since TNF modulates both cardiac contractility and peripheral resistance, the two most important haemodynamic determinants of cardiac function. Thus, increased levels of TNF or of its soluble receptors have been implicated in the pathophysiology of ischaemia-reperfusion injury, myocarditis, cardiac allograft and, more recently, also in the progression of congestive heart failure. In this later condition, TNF could be responsible for further ventricular remodelling; down-regulation of myocardial contractility; increased rate of apoptosis of the endothelial cell and of the myocytes, alteration of the expression and function of the enzymes regulating nitric oxide production and, of course, the induction of cachexia resulting in further peripheral muscle dysfunction. The hypothesis that TNF may be involved in the progression of CHF may be of clinical relevance as anti-TNF strategies are considered for therapeutical strategies. The purposes of this article are: (1) to define the physiological aspects of TNF; (2) to outline the specific function of TNF within the heart; (3) to consider the role of TNF in CHF; and (4) to speculate on possible anti-TNF treatment. (C) 1999 Academic Press.