Tumor necrosis factor alpha (TNF-α) is a pleiotropic cytokine produced by inflammatory cells and is a mediator of systemic response to sepsis and injury. Recently, it has been reported that circulating TNF-α is increased in patients with severe heart failure. This activation may have either beneficial or injurious effects. Possibly, one of the favorable events that TNF-α triggers is the synthesis of an inducible isoform of the nitric oxide (NO)-synthase in various cell types, such as macrophages, endothelial cells, and smooth muscle cells. As a consequence, the increased availability of NO in peripheral vessels could counterbalance the impaired vasodilatory response observed after infusion of acetylcholine in patients with congestive heart failure. However such an activation may be detrimental to the heart, as it is now recognized that TNF-α has a negative inotropic effect that is reversible by L-NMMA, an L-arginine analogue that inhibits NO-synthase activity. Furthermore, TNF-α is able to prime programmed cell death or apoptosis when interacting with its membrane receptors. This effect would be of great relevance in the progression of deterioration of heart function. TNF receptors, besides mediating its multifaceted activity, are able to modulate its access to the cell surface, when present in a soluble form in the blood. Soluble TNF receptors have been found elevated in. severe heart failure. The pathophysiological significance of this increase is still unclear and requires further investigations.
|Number of pages||8|
|Publication status||Published - 1995|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine