Synergistic effects of interleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha: Central monoamine, corticosterone, and behavioral variations

The proinflammatory cytokines interleukin-1 beta (IL-1 beta), IL-6, and tum or necrosis factor-alpha (TNF-alpha) influence neurodoendocrine activity, p romote central neurotransmitter alterations, and induce a constellation of symptoms collectively referred to as sickness behaviors. These cytokines ma y also elicit anxiety and disturbances in humans. In the present investigat ion, systemic IL-1 beta and TNF-alpha dose-dependently and syngergistically distributed consumption of highly palatable food source (chocolate milk), possibly reflecting anorexia or anhedonia endangered by the treatments. As well, these cytokines synergistically increased plasma corticosterone level s. Although IL-1 beta and TNF-alpha provoked variations of amine turnover i n the hypothalanus, locus coeruleus, and central amygdala, synergistic effe cts were not evident in this respect. Nevertheless, in view of the central amine variations induced by the cytokines, it is suggested that immune acti vation may come to influence complex behavioral processes as well as affect ive state. (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.