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Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta.
Anforth, H, Bluthe, R, Bristow, A, Hopkins, S, Lenczowski, M, Luheshi, G, Lundkvist, J, Michaud, B, Mistry, Y, Van Dam, A, Zhen, C, Dantzer, R, Poole, S, Rothwell, NJ, Tilders, F, Wollman, E
Eur Cytokine Netw. 1998;9( 3):279-88.
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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.
Keyword(s)
Animals; Cloning, Molecular; Escherichia coli; Human; Injections, Intraventricular; Insulinoma; Male; Mice; Pancreatic Neoplasms; Rats; Rats, Sprague-Dawley; Social Behavior; Tumor Cells, Cultured; administration & dosage: Interleukin-1; administration & dosage: Recombinant Proteins; drug effects: Body Temperature; drug effects: Brain; drug effects: Cerebral Ventricles; drug effects: Exploratory Behavior; drug effects: Gene Expression Regulation, Neoplastic; drug effects: Hypothalamo-Hypophyseal System; drug effects: Pituitary-Adrenal System; drug effects: Transcription, Genetic; genetics: Tumor Necrosis Factor; physiology: Receptors, Interleukin-1