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 Printable version |
Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta. |
European Cytokine Network. Volume 9, Number 3, 279-88, September 1998, Articles originaux
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 Free Article
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Author(s) : H.R. ANFORTH, R.M. BLUTHE, A. BRISTOW, S. HOPKINS, M.J.P. LENCZOWSKI, G. LUHESHI, J. LUNDKVIST, B. MICHAUD, Y. MISTRY, A.M. VAN DAM, C. ZHEN, R. DANTZER, S. POOLE, N.J. ROTHWELL, F.J.H. TILDERS, E.E. WOLLMAN |
Summary : 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. |
Keywords : rat, IL-1alpha, IL-1beta, binding affinity, TNF-alpha, fever, ACTH, corticosterone, behaviour. |
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