Role of Tumor Necrosis Factor in Protein Metabolism

The relentless catabolism of body protein during chronic disease may kill. Early investigators presumed that the origins of cachexia lay in the underlying neoplasia or organism usurping the host's energy stores. More recent evidence indicates that immunological and neuroendocrinological mediators produced in response to invasion amplify the catabolism of lean body tissue, diverting substrate from peripheral tissues to liver as part of an acute-phase response. Anorexia and decreased food intake invariably accompany catabolic illnesses, but unlike the metabolic adaptation that occurs during unstressed fasting, the cachectic host fails to downregulate muscle protein catabolism and urinary nitrogen losses, and persistently excretes up to 15 g of nitrogen per day. Since mammals lack a protein storage depot, loss of body protein is associated with loss of function, resulting in immunosuppression, weakness, delayed wound healing, decreased tolerance for surgical and chemotherapeutic regimens, and death.