TUMOR-NECROSIS-FACTOR AND CACHEXIA - A CURRENT PERSPECTIVE

Anorexia, net proteolysis of skeletal muscle and consumption of body f at are hallmarks of the cachexia syndrome associated with chronic dise ase states. While inanition contributes to cachexia, this wasting diat hesis has little in common with simple starvation. The cachexia syndro me is characterized by progressive weight loss and depletion of lean b ody mass in excess to that resulting from comparable caloric restricti on. Accelerated mobilization and consumption of host protein stores fr om peripheral tissues occurs to support gluconeogenesis and acute phas e protein synthesis [1,2]. In contrast, simple starvation is associate d with a relative sparing of lean tissue with the preferential consump tion of fat. While the clinical manifestations of cachexia are readily apparent, identification of the specific mechanisms responsible for t he development of cachexia remains an enigma. In recent years, interes t has focused on the role that the immune system plays in the developm ent of cachexia. Investigators initially hypothesized that the chronic production of two inflammatory cytokines, tumour necrosis factoralpha (TNFalpha) and/or interleukin-1 (IL-1), could explain the host non-sp ecific responses resulting in cachexia [3-5]. Other pro-inflammatory c ytokines, including interleukin-6 (IL-6) [6,7] and interferon-gamma [8 , 9], have been more recently proposed to be involved in this complex process. Although no consensus exists for the exclusive role of any on e cytokine in the pathogenesis of cachexia, there is growing acceptanc e that the progression of cachexia results in part from the inappropri ate release of one or more pro-inflammatory cytokines [10, 11]. In the present review, the current role of TNFalpha as a mediator of cachexi a is examined.