Key to 'wasting syndrome'

A reduction in albumin production can cause of cachexia in patients with cancer or chronic inflammatory conditions, but the mechanism behind this inhibition remains unknown. In December 3 European Molecular Biology Organization Journal, Martina Buck and colleagues from VA San Diego Healthcare System and University of California, San Diego, show that tumor necrosis factor alpha (TNF-α) is the key molecule in the prevention of albumin production in chronic diseases.

Buck et al. observed that TNF-α treatment of primary mouse hepatocytes or TNF-α overexpression in a murine model of cachexia inhibits transcription of the albumin gene by increasing oxidative stress, nitric oxide synthase expression (NOS) and phosphorylation of C/EBPβ on Ser239. In addition, they showed that treatment of TNF-α mice with antioxidants or NOS inhibitors prevented phosphorylation of C/EBPß on Ser239, and rescued the albumin production (EMBO J 2001, 20:6712-6723).

Antioxidants (such as vitamin E) might halt wasting in humans if ...