Neuropeptide Y Counteracts Interferon-Alpha-Induced Anorexia

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.

Cytokines and feeding

“…9 Neuropeptide Y blocks cytokine-induced anorexia, and cytokines block neuropeptide Y-induced feeding, that is cytokine-neuropeptide Y interactions are antagonistic. 10,11 The best characterized examples are the NPY-induced inhibition or blockage of anorexia induced by interleukin-1 beta, interferon-alpha, ciliary neurotrophic factor, and leptin. Endogenous cytokine-peptide interactions relevant to feeding control include reciprocal cytokine-leptin-neuropeptide Y-CRH-glucocorticoid interactions.…”

Inflammatory Cytokines and Antipsychotic-Induced Weight Gain: Review and Clinical Implications

“…The anorexigenic outcomes of the APR can be mimicked by externally administering inflammatory cytokines to the periphery or CNS, with synergistic effects occurring between cytokines in some cases [78,79,80,81,82,83,84,85,86]. The resultant alterations in feeding behaviours are typically observed as reductions in meal size, duration, and frequency, and longer inter-meal intervals [80,85,87].…”

The role of genetic variation across IL-1β, IL-2, IL-6, and BDNF in antipsychotic-induced weight gain

“…Inflammatory cytokines, such as IL-1, IL-1, IL-2, IL-6, IL-8, TNF-, and IFNs have been shown to suppress food intake, both individually and synergistically, after peripheral and central administration [342][343][344][345][346][347][348][349][350] 352 showed that rats treated with IL-1 had a reduced total caloric intake, and consumed relatively more carbohydrates and less protein. Taste aversion can also result from cytokine administration but this does not appear to be a major component of anorexic action 336,353 .…”