[The role of TNF-alpha in the etiopathogenesis of heart failure].

Clinical evidence demonstrates participation of several cytokines in cardiac heart failure pathogenesis, in particular tumor necrosis factor-alpha (TNF-alpha), which induces left ventricular dysfunction, acute pulmonary edema and congestive cardiomyopathy. Increased levels of TNF-alpha in patients with heart failure were proved and may have prognostic significance. Absent in normal myocardium, produced in the myocardium in response to volume overload, TNF-alpha can depress cardiac function directly and indirectly by induction of nitric oxide synthase produced by macrophages, cardiac myocytes and other cells. The most of TNF-alpha effects are performed by two receptors termed as TNF-RI and TNF-RII identified on the surface of many cells. The extracellular domain fragments of both receptors shed from cell surface can be detected as soluble forms sTNF-RI and sTNF-RII in the urine and blood, and their blood levels in patients with severe heart failure are elevated. There are various pharmacological agents that block the biological effects of TNF-alpha, however only two of them have been used in patients with heart failure: pentoxifylline and etanercept. Encouraging effects of this studies must be regarded as provisional because of relatively small numbers of treated patients. Preliminary results of other randomized, multicenter and in large patients populations trials, planned till 2002 year indicate the possibility of novel anti-TNF strategies in heart failure; treatment is well tolerated and can be effective. It is thought, that recombinantly produced TNF-alpha soluble receptor being now evaluated clinically can determine the progress in heart failure treatment.