Interleukin-1beta mediates the memory impairment associated with a delayed type hypersensitivity response to bacillus Calmette-Guérin in the rat hippocampus.
Interleukin-1beta (IL-1beta) plays a major role in the initiation and exacerbation of brain inflammation, and its action is limited by the natural antagonist of IL-1 receptors, IL-1Ra. The aim of the present study was to test the hypothesis that IL-1beta mediates the functional consequences of inflammation during the course of delayed-type hypersensitivity response to bacillus Calmette-Guérin (BCG) in the hippocampus of Lewis rats. Animals were primed with an injection of BCG in the right hippocampus and challenged 4 weeks later with BCG administered subcutaneously. Concentrations of IL-1beta and IL-1Ra were measured by ELISA in the BCG injected hippocampus and compared to those measured in the contralateral hippocampus during the first 2 weeks post-challenge. IL-1beta levels increased in response to BCG challenge and peaked 12 days after challenge. The same variations appeared in the contralateral hippocampus but to a lesser extent. Hippocampal IL-1Ra levels increased in response to intrahippocampal injection of BCG. They further increased at days 6 and 9 post-challenge and decreased from day 12 back to baseline values on day 16. The increase in IL-1beta levels and the decline in IL-1Ra levels were associated with an impairment in spatial memory in a Y-maze on day 16 post-challenge, that was abrogated by chronic administration of IL-1Ra via a subcutaneously implanted osmotic minipump geared to deliver 7 mg IL-1Ra/day. These results show that overexpression of IL-1beta in the brain during the course of a chronic inflammation has deleterious consequences on cognitive processes, that are reversed by blockade of IL-1 receptors.
Palin
Karine
K
INRA-UMR 1244--Université V. Segalen Bordeaux 2, FRE CNRS Institut François Magendie, Rue Camille Saint-Saëns, 33077 Bordeaux, France.
Bluthé
Rose-Marie
RM
Verrier
Danièle
D
Tridon
Viviane
V
Dantzer
Robert
R
Lestage
Jacques
J
D000818:Animals; D004195:Disease Models, Animal; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D006624:Hippocampus / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000276:immunology*; D009163:Mycobacterium bovis / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew; D012795:Sialoglycoproteins / Q000378:metabolism
D018836:Inflammation Mediators; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins