Neuropeptide Y Counteracts Interferon-Alpha-Induced Anorexia

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Abstract
Interferon-α (IFN-α) 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-α-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-α-induced anorexia in rats. The results show that IFN-α induced significant anorexia when administered centrally into the third cerebral ventricle at an immunotherapeutically relevant dose (1,350 IU/rat). Heat-inactivated IFN-α had no effect. NPY (5.0 µg/rat) counteracted the IFN-α-induced anorexia when administered 3 or 10 h following IFN-α, or when it was concomitantly administered with IFN-α. The data suggest that NPY and its agonists could represent a potential novel intervention for IFN-α immunotherapy-associated anorexia.