Anticytokine approaches to the treatment of anorexia and cachexia

Proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha) have a prominent role in the pathogenesis of anorexia and cachexia of chronic disease. Pentoxyfylline and thalidomide are inhibitors of TNF-alpha that have been tried as rational therapeutic interventions in cachexia. Preliminary studies with pentoxyfylline have not shown efficacy in reversing weight loss, despite evidence of TNF-alpha inhibition. In contrast, the administration of thalidomide to patients with human immunodeficiency virus- and/or tuberculosis-associated weight loss has consistently resulted in weight gain. However, the relationship of the metabolic benefits of thalidomide treatment to its complex effects on the immune system is imperfectly understood. Studies of thalidomide, either alone or in combination with other therapies for the treatment of cancer cachexia, are warranted.