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Time for primary review 32 days. Tumour necrosis factor alpha (TNFα) is a pleiotropic cytokine that has many proinflammatory actions with negative inotropic effects. It has been implicated in the pathogenesis of many non-infectious disorders, from rheumatoid disease [1], to multiple sclerosis [2]. This cytokine also affects the heart [3] where it is produced by immune cells and the myocardium in some diseases. Raised serum TNFα is seen in patients with cardiomyopathy, myocardial infarction, and chronic heart failure [4], thus implicating TNFα in disease pathogenesis. Raised serum levels of this cytokine have also been identified in transplant patients following episodes of acute cellular rejection. There is a correlation between TNFα expression and rejection grade [5] suggesting that the cytokine is a candidate marker of rejection.In this review, we consider the basic biology of TNFα in relation to certain cardiac diseases. There are interrelationships between some of the conditions described, but these have been arbitrarily divided into three main groups: allograft rejection, coronary artery disease, and heart failure.Tumor necrosis factor alpha, cachectin (TNFα), was originally identified for its potent toxicity against tumour cells, hence its name [6]. Today, TNFα is recognised as a pleiotropic cytokine functioning within a complex and tightly regulated cytokine network. It activates multiple transduction pathways, inducing or suppressing a wide variety of genes, including those encoding the production of cytokines, adhesion molecules, and inducible nitric oxide synthase (iNOS). TNFα has many proinflammatory actions: orchestrating the inflammatory response through activation of proinflammatory cytokine genes, such as IL-1 and IL-6, as well as its own production [7]. This section will summarise our current understanding of the biology and function of TNFα with particular emphasis on the heart, and review recent work on the regulation of its production.### 2.1 TNFα moleculeThe TNFα molecule (a 157 … * Corresponding author. Tel.: +44-161-282-1261; fax: +44-161-718-7167

Tumour necrosis factor alpha and the cardiovascular system: its role in cardiac allograft rejection and heart disease