Effect of cytokines on hypothalamic neuropeptide Y release in vitro

Studies involving altered energy balance states in rodents have demonstrate d that hypothalamic neuropeptide Y (NPY) activity is strongly activated in states of negative energy balance, such as periods of dietary restriction o r starvation, However, in cancer cachexia, when there is a significant redu ction in body weight as a result of appetite loss, leading to loss in fat a nd lean tissue mass, there is no augmentation in the activity of the hypoth alamic NPY system. Therefore, we have examined whether cytokines, interleuk in (IL)-1, IL-1 beta, IL-6, and tumor-necrosis factor-alpha (TNF-alpha; cac hectin), which are elevated in cancer patients, can attenuate NPY release f rom hypothalamic slices in vitro. None of the cytokines altered either the basal or stimulated NPY release from the hypothalamic slices. However, we w ere able to measure a significant reduction in potassium stimulated NPY rel ease (-60%) by using the nonselective voltage-dependent calcium channel blo cker NiCl (30 mu M) without any effect on basal release, as a positive cont rol Therefore, we suggest that the Failure to activate the hypothalamic NPY system in states of cancer cachexia cannot be attributed to a cytokine-ind uced reduction in neurotransmitter release. (C) 2000 Elsevier Science Inc. All rights reserved.