Interleukin-1beta mediates the memory impairment associated with a delayed type hypersensitivity response to bacillus Calmette-Guérin in the rat hippocampus

• Published in: Brain, behavior, and immunity Vol. 18; no. 3; pp. 223 - 230
• Main Authors: Palin, Karine, Bluthé, Rose-Marie, Verrier, Danièle, Tridon, Viviane, Dantzer, Robert, Lestage, Jacques
• Format: Journal Article
• Language: English
• Published: Netherlands 01.05.2004
• Subjects: Animals; Disease Models, Animal; Encephalitis - immunology; Encephalitis - metabolism; Encephalitis - microbiology; Hippocampus - immunology; Hippocampus - metabolism; Hippocampus - microbiology; Hypersensitivity, Delayed - immunology; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Interleukin 1 Receptor Antagonist Protein; Interleukin-1 - immunology; Interleukin-1 - metabolism; Maze Learning - physiology; Memory Disorders - immunology; Mycobacterium bovis - immunology; Rats; Rats, Inbred Lew; Sialoglycoproteins - metabolism
• ISSN: 0889-1591

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.