The Role of Tumor Necrosis Factor Alpha Blockade in the Treatment of Congestive Heart Failure

Abstract

The experimental evidence in support of the role of tumor necrosis factor in heart failure stems from the observations that tumor necrosis factor exerts negative inotropic effects and is capable of promoting fibrosis, hypertrophy, and cardiomyopathy in animal models. More importantly, cardiac specific tumor necrosis factor levels are regulated by pressure and volume load in animals and in humans. Therefore, a series of clinical small trials were conducted with etanercept, a highly specific anti‐tumor necrosis factor‐blocking agent that indicated a potential therapeutic role. However, two large randomized clinical trials powered to determine the effect of etanercept and infliximab on mortality have demonstrated no clinical benefit. The explanation of those findings are not clear; however, based on the strength of the experimental evidence one can conclude that perhaps other nonspecific approaches to manipulate the immune system may be of benefit.

Subclinical cardiovascular disease and it's improvement after long‐term TNF‐α inhibitor therapy in severe psoriatic patients

“…Experimental data suggest that in mammalian cardiomyocytes TNF‐α exerts a negative inotropic effect, increases apoptosis and enhances hypertrophy, interstitial cellular infiltration and myocardial fibrosis. Moreover, TNF‐α contributes to myocardial remodelling by reducing responsiveness to beta 1 ‐adrenergic stimulation and increasing atrial natriuretic factor production by the myocardium …”

“…Moreover, TNF-a contributes to myocardial remodelling by reducing responsiveness to beta 1 -adrenergic stimulation and increasing atrial natriuretic factor production by the myocardium. [27][28][29] Taking into account that patients with severe CHF are characterized by high serum and myocardial TNF-a levels and that the magnitude of TNF-a elevation is correlated with ventricular dysfunction, 30,31 it is not surprising that TNF-a inhibition can improve cardiac function.…”

Infliximab in the treatment of rheumatoid arthritis

“…Anti-TNFα therapies have been associated with congestive heart failure and these biological treatments are contra-indicated in patients with a history of NYHA III or IV heart failure 74,88. An increase in the liver function test, and pancytopenia, has also been associated with anti-TNFα use 64.…”

“Cytokine” Model of Pathogenesis of Chronic Heart Failure and the Opportunities of New Therapeutic Strategy in Decompensated Patients

“…В настоящее время существует много лекарственных средств, обладающих способностью ингибировать синтез ФНО-α in vitro и in vivo [31,35,44,47].…”