Biological activity and brain actions of recombinant rat interleukin-1alpha and interleukin-1beta
| Autor: | H R, Anforth, R M, Bluthe, A, Bristow, S, Hopkins, M J, Lenczowski, G, Luheshi, J, Lundkvist, B, Michaud, Y, Mistry, A M, Van Dam, C, Zhen, R, Dantzer, S, Poole, N J, Rothwell, F J, Tilders, E E, Wollman |
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| Rok vydání: | 1998 |
| Předmět: |
Male
Hypothalamo-Hypophyseal System Transcription Genetic Tumor Necrosis Factor-alpha Brain Pituitary-Adrenal System Receptors Interleukin-1 Recombinant Proteins Body Temperature Cerebral Ventricles Rats Gene Expression Regulation Neoplastic Pancreatic Neoplasms Rats Sprague-Dawley Mice Escherichia coli Exploratory Behavior Tumor Cells Cultured Animals Humans Insulinoma Cloning Molecular Social Behavior Injections Intraventricular Interleukin-1 |
| Zdroj: | European cytokine network. 9(3) |
| ISSN: | 1148-5493 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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