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.