Biological activity and brain actions of recombinant rat interleukin-1α and interleukin-1β

Helen R. Anforth, Rose Marie Bluthe, Adrian Bristow, Steve Hopkins, Marik J.P. Lenczowski, Giamal Luheshi, Johan Lundkvist, Bruno Michaud, Yogesh Mistry, Anne Marie Van Dam, Chai Zhen, Robert Dantzer, Steeve Poole, Nancy J. Rothwell, Fred J.H. Tilders, Emmanuelle E. Wollman

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94 Scopus citations

Abstract

IL-1α and IL-1β 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-1α and IL-1β 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-1α and IL-1β in the rat system as a first step to dissect out the mechanisms that are involved in these effects. In vitro, recombinant rat IL-1α and IL-1β 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-α mRNA. In vivo, recombinant rat IL-1α and IL-1β enhanced body temperature, increased plasma levels of corticosterone and ACTH, and depressed social behaviour. All these effects were obtained at doses 100-1000 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-1α and IL-1β 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 (US)
Pages (from-to)279-288
Number of pages10
JournalEuropean Cytokine Network
Volume9
Issue number3
StatePublished - Nov 19 1998

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Keywords

  • ACTH
  • Behaviour
  • Binding affinity
  • Corticosterone
  • Fever
  • IL-1α
  • IL-1β
  • Rat
  • TNF-α

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Clinical Biochemistry

Cite this

Anforth, H. R., Bluthe, R. M., Bristow, A., Hopkins, S., Lenczowski, M. J. P., Luheshi, G., Lundkvist, J., Michaud, B., Mistry, Y., Van Dam, A. M., Zhen, C., Dantzer, R., Poole, S., Rothwell, N. J., Tilders, F. J. H., & Wollman, E. E. (1998). Biological activity and brain actions of recombinant rat interleukin-1α and interleukin-1β. European Cytokine Network, 9(3), 279-288.