Neuropeptide Y counteracts interferon-alpha-induced anorexia

Interferon-alpha (IFN-alpha) immunotherapy is associated with significant adverse neurological effects, including anorexia, which can be a limiting factor in immunotherapy. Thus, it is important to develop strategies that could ameliorate IFN-alpha-induced neurological manifestations without significantly affecting its immunomodulating properties. In this study, we tested the hypothesis that an endogenous feeding-enhancing peptide, neuropeptide Y (NPY), could inhibit IFN-alpha-induced anorexia in rats. The results show that IFN-alpha induced significant anorexia when administered centrally into the third cerebral ventricle at an immunotherapeutically relevant dose (1,350 IU/rat). Heat-inactivated IFN-alpha had no effect. NPY (5.0 microg/rat) counteracted the IFN-alpha-induced anorexia when administered 3 or 10 h following IFN-alpha, or when it was concomitantly administered with IFN-alpha. The data suggest that NPY and its agonists could represent a potential novel intervention for IFN-alpha immunotherapy-associated anorexia.