Effect of cytokines on hypothalamic neuropeptide Y release in vitro

Studies involving altered energy balance states in rodents have demonstrated that hypothalamic neuropeptide Y (NPY) activity is strongly activated in states of negative energy balance, such as periods of dietary restriction or starvation. However, in cancer cachexia, when there is a significant reduction in body weight as a result of appetite loss, leading to loss in fat and lean tissue mass, there is no augmentation in the activity of the hypothalamic NPY system. Therefore, we have examined whether cytokines, interleukin (IL)-1, IL-1beta, IL-6, and tumor-necrosis factor-alpha (TNF-alpha; cachectin), which are elevated in cancer patients, can attenuate NPY release from hypothalamic slices in vitro. None of the cytokines altered either the basal or stimulated NPY release from the hypothalamic slices. However, we were able to measure a significant reduction in potassium-stimulated NPY release (-60%) by using the nonselective voltage-dependent calcium channel blocker NiCl (30 microM) without any effect on basal release, as a positive control. Therefore, we suggest that the failure to activate the hypothalamic NPY system in states of cancer cachexia cannot be attributed to a cytokine-induced reduction in neurotransmitter release.