Anorexia induced by chronic central administration of cytokines at estimated pathophysiological concentrations

Carlos R. Plata-Salamán, Gayatri Sonti, Jeffrey P. Borkoski, Charlie D. Wilson, Jarlath M.H. Ffrench-Mullen

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Abstract

Interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) induce acute anorexia by direct action in the central nervous system (CNS) at estimated pathophysiological concentrations reported in the cerebrospinal fluid (CSF). Cytokine-induced anorexia may also participate in the long-term anorexia observed during disease. Here, we studied the effects of chronic intracerebroventricular (ICV) microinfusion (through osmotic minipumps) of various cytokines on feeding and drinking in rats. The results show: IL-1β decreased nighttime feeding dose-dependently (with 0.5, 1.0, 2.0, and 8.0 ng/24 h, n ≤ 8/group). The decrease of feeding and corresponding decrease of body weight persisted during the 7-day infusion. Total daily food intake decrease was less prominent relative to the nighttime decrease because daytime food intake slightly increased. Feeding and body weight increased toward baseline following the end of the IL-1β infusion. ICV microinfusion of heat-inactivated IL-1β or IL-1β plus IL-1 receptor antagonist had no effect, suggesting specificity of action of IL-1β. Water intake did not decrease in any IL-1β-treated group, suggesting specificity on feeding. Chronic ICV administration of TNF-α (20, 100, or 300 ng/24 h), IL-6 (100 ng/24 h), or IL-8 (20 ng/24 h) was significantly less effective than IL-1β in inducing behavioral modifications. The results suggest that IL-1β, at doses that yield estimated pathophysiological concentrations in the CSF, is capable of inducing long-term anorexia and this effect may participate in the anorexia observed during chronic disease.

Original languageEnglish (US)
Pages (from-to)867-875
Number of pages9
JournalPhysiology and Behavior
Volume60
Issue number3
DOIs
Publication statusPublished - Sep 1996

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Keywords

  • Behavior
  • Cerebrospinal fluid
  • Feeding and drinking
  • Food and water intake
  • Growth factor
  • Immune system
  • Immunomodulator
  • Interleukin
  • Intracerebroventricular administration
  • Nervous system
  • Neuroimmunology
  • Osmotic minipump
  • Rat
  • Tumor necrosis factor

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Behavioral Neuroscience

Cite this

Plata-Salamán, C. R., Sonti, G., Borkoski, J. P., Wilson, C. D., & Ffrench-Mullen, J. M. H. (1996). Anorexia induced by chronic central administration of cytokines at estimated pathophysiological concentrations. Physiology and Behavior, 60(3), 867-875. https://doi.org/10.1016/S0031-9384(96)00148-5