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Issue 840 coverNEUROIMMUNOMODULATION: MOLECULAR ASPECTS, INTEGRATIVE SYSTEMS, AND CLINICAL ADVANCES Copyright © 1998 by the New York Academy of Sciences
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Articles by VAN DAM, A.-M.
Articles by TILDERS, F. J. H.
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Articles by VAN DAM, A.-M.
Articles by TILDERS, F. J. H.
Annals of the New York Academy of Sciences 840:128-138 (1998)
© 1998 New York Academy of Sciences

Effects of Peripheral Administration of LPS on the Expression of Immunoreactive Interleukin-1{alpha}, ß, and Receptor Antagonist in Rat Brain

ANNE-MARIE VAN DAMa,b, STEPHEN POOLEc, MARIANNE SCHULTZBERGd, FLORA ZAVALAe AND FRED J. H. TILDERSb

bResearch Institute Neurosciences Free University, Medical Faculty, Department of Pharmacology, 1081 BT Amsterdam, the Netherlands
cNIBSC, Potters Bar, Hertfordshire EN6 3QG, United Kingdom
dKarolinska Institute Division of Geriatric Medicine, S-14186 Huddinge, Sweden
eINSERM U25, Hopital Necker, 75743 Paris, France

aFax: 31-20-4448100; e-mail: amw.van_dam.pharm{at}med.vu.nl

The cytokine interleukin-1 (IL-1) appears to play a pivotal role in the orchestration of brain-mediated, nonspecific illness symptoms during an infection. In the present study, we examine the possibility that IL-1 is produced in the central nervous system itself, which may be responsible for the induction of brain-mediated responses. Using immunocytochemical techniques, we demonstrated that peripheral administration of bacterial endotoxin to rats caused a time- (1.5-24 hr) and dose-dependent (4µg/kg-2.5 mg/kg) induction of IL 1ß immunoreactivity in cells identified as macrophages in meninges and choroid plexus and microglial cells in various brain regions. At 8 hr after endotoxin (2.5 mg/kg), immunoreactive IL-1{alpha} was observed in the same areas and cell types as IL-1ß. Although no quantitative measurements have been performed, it appears that fewer cells express immunoreactive IL-1{alpha} than IL-1ß. Furthermore, IL-1ra was found to be constitutively expressed in neurons in the paraventricular nucleus and supraoptic nucleus, which is in accordance with mRNA data. After administration of endotoxin, we observed no additional cells that expressed immunoreactive IL-1ra. We conclude that IL-l{alpha} and IL-1ß production in the brain is induced in the same cell types, whereas IL-lra is expressed consititutively by a different cell type-probably neurons.




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