Cytokines and Cardiomyocyte Death

Cytokines have been associated with the pathogenesis of acute coronary syndromes and chronic heart failure (CHF), which are both associated with cardiomyocyte loss.In CHF, increased serum concentrations of proinflammatory cytokines, including tumour necrosis factor a (TNF-a) and also soluble TNF receptor have been found.Both TNF and Fas-ligand have been able to induce programmed cell death (apoptosis) of cardiomyocytes in various experimental studies.In ischaemic conditions of the heart, increased serum levels of soluble Fas receptor have been found.The proinflammatory cytokines interleukin 1 (IL-l), 11-2 and interferon-y can induce TNF production from target cells, including myocytes.TNF and some other cytokines are able to induce nitric oxide production, which depresses cardiac function and can induce apoptosis.However, anti-inflammatory cytokines such as IL-10, 11-4 and 11-13, secreted by T-helper type 2 lymphocytes and other cells, inhibit the production of proinflammatory cytokines.Preliminary studies suggest that cardiotrophin-1 , produced by cardiomyocytes, is able to inhibit cytokine-induced cardiomyocyte apoptosis in vitro.As growth hormone is able to inhibit the production of proinflammatory cytokines in many cell types, it may also play an important role in the regulation of apoptosis induced by these cytokines.When the cytokine-induced pathways leading to altered gene expression of cardiomyocytes are understood, this knowledge may aid in the development of drugs that prevent progressive cardiomyocyte loss, in particular by inhibiting cytokine-induced apoptosis.