The role of tumor necrosis factor alpha blockade in the treatment of congestive heart failure.

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.