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

Eur Cytokine Netw. 1998 Sep;9(3):279-88.


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.

MeSH terms

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


  • Interleukin-1
  • Receptors, Interleukin-1
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha