Role and significance of the cytokines in the developing of cardiac failure.

The hypothesis of immunitory and inflammatory activation occurring during c hronic cardiac failure, capable of maintaining the disease, is supported by many experimental and clinical trials. Plasma cytokinines levels, particul arly the tumour necrosis factor alpha (TNF alpha), are raised at advanced s tages of the disease, especially in cachectic patients. The correlations wi th other, more traditional markers, especially neurohumoral, are not very c lose, probably suggesting different mechanisms. Cytokinines are a group of very different molecules with multiple, non-specific, and even beneficial e ffects. However, the lack of regulation in severe cardiac failure may lead to deleterious effects on the heart. The experimental effects of TNF alpha (mini-pumps, transgenic animals) include features of myocarditis, chamber d ilatation and contractile dysfunction. Large scale therapeutic trials of lo ng acting TNF alpha antagonists could confirm the "inflammation hypothesis" of mutual interaction between cardiac failure and the production of cytoki nines.