Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta.

H Anforth, R Bluthe, A Bristow, S Hopkins, M Lenczowski, G Luheshi, J Lundkvist, B Michaud, Y Mistry, A Van Dam, C Zhen, R Dantzer, S Poole, NJ Rothwell, F Tilders, E Wollman

Research output: Contribution to journalArticlepeer-review

Abstract

IL-1alpha and IL-1beta have potent effects on the central nervous system resulting in fever, activation of the hypothalamic-pituitary-adrenal axis and behavioural depression. These effects have mainly been studied in rats, using recombinant human and mouse IL-1. Because IL-1alpha and IL-1beta show some species specificity in the potency of their biological activities, the objective of the present work was to directly compare the effects of recombinant rat IL-1alpha and IL-1beta in the rat system as a first step to dissect out the mechanisms that are involved in these effects. In vitro, recombinant rat IL-1alpha and IL-1beta bound with the same affinity as human IL-1 to the rat insulinoma Rin m5F cell line that mainly expresses type I IL-1 receptors. This binding activated IL-1 receptors, as shown by induction of the synthesis of TNF-alpha mRNA. In vivo, recombinant rat IL-1alpha and IL-1beta enhanced body temperature, increased plasma levels of corticosterone and ACTH, and depressed social behaviour. All these effects were obtained at doses 100-1,000 fold lower when IL-1 was injected centrally than when it was administered peripherally, indicating that they are centrally mediated. The relative potencies of recombinant rat IL-1alpha and IL-1beta were not the same depending on the endpoint and the route of injection, indicating that different mechanisms are likely to be involved in the various effects of IL-1 on the brain.
Original languageEnglish
JournalEuropean Cytokine Network
Volume9( 3)
Publication statusPublished - Sept 1998

Keywords

  • Animals
  • drug effects: Body Temperature
  • drug effects: Brain
  • drug effects: Cerebral Ventricles
  • Cloning, Molecular
  • Escherichia coli
  • drug effects: Exploratory Behavior
  • drug effects: Gene Expression Regulation, Neoplastic
  • Human
  • drug effects: Hypothalamo-Hypophyseal System
  • Injections, Intraventricular
  • Insulinoma
  • administration & dosage: Interleukin-1
  • Male
  • Mice
  • Pancreatic Neoplasms
  • drug effects: Pituitary-Adrenal System
  • Rats
  • Rats, Sprague-Dawley
  • physiology: Receptors, Interleukin-1
  • administration & dosage: Recombinant Proteins
  • Social Behavior
  • drug effects: Transcription, Genetic
  • Tumor Cells, Cultured
  • genetics: Tumor Necrosis Factor

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