Recent Insights into the Role of Tumor Necrosis Factor in the Failing Heart

Abstract

Recent clinical and experimental studies have identified the importance of ‘neurohormones’ as biological mediators and/or modifiers of left ventricular remodeling and disease progression in the failing heart. This insight has, in turn, provided the rationale basis for antagonizing the activation of neurohormonal systems (e.g. the renin angiotensin system and the adrenergic system) in the setting of heart failure. In addition to neurohormones, it has become apparent that another portfolio of biologically active molecules, termed cytokines, are expressed along with the neurohormones in the setting of heart failure. The current interest in understanding the role or pro-inflammatory cytokines, such as tumor necrosis factor (TNF), in heart failure relates to the observation that many aspects of the syndrome of heart failure can be explained by the (Table 1). Simply stated, when expressed at sufficiently high concentrations, TNF mimics some aspects of the so-called heart failure phenotype, including (but not limited to) progressive left ventricular (LV) dysfunction, pulmonary edema, LV remodeling, fetal gene expression and cardiomyopathy. Thus the elaboration of TNF, much like the elaboration of neurohormones, may represent a biological mechanism that is responsible for producing symptoms in patients with heart failure. In the present discussion, we will review several important areas that are directly relevant to the role of TNF as a mediator of disease progression in the failing heart, including a brief overview of the biology of TNF, followed by a discussion of the deleterious effects of TNF on LV remodeling effects, and finally a review of the clinical studies that link TNF production to disease progression in heart failure.