19:10 - 21:00
Poster Session 1 ‟Innate immunity and infection”
Room: Ishikawa Ongakudō Interchange Hall
Poster Session
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The role of the IL-1 receptor in the centrally-elicited sickness response to lipopolysaccharide.
Takashi Matsuwaki1, 2, Kiseko Shionoya1, Robert Ihnatko1, Anna Eskilsson1, Shigeru Kakuta3, Sylvie Dufour4, Markus Schwaninger5, Ari Waisman6, Werner Müller7, Emmanuel Pinteaux7, David Engblom1, Anders Blomqvist1
1Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden, 2Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan, 3Department of Biomedical Science, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan, 4Institut Curie/CNRS UMR144, Paris, France, 5Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany, 6Institute for Molecular Medicine, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany, 7Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom

Peripheral immune stimuli are signaled to the central nervous system to induce various kinds of sickness responses, such as anorexia, stress hormone release and fever. The proinflammatory cytokine interleukin-1β (IL-1β) has been suggested to play a major role in this signal transduction. In the present study we first compared the centrally elicited immune responses to lipopolysaccharide (LPS) between IL-1 receptor (IL-1R1) KO mice and wild-type (WT) mice. After LPS injection, food intake was monitored every 3h. To evaluate the responsibility of HPA-axis to LPS, plasma concentrations of corticosterone and ACTH were determined at 1, 3 and 6 h after injection, and immunostaining for c-Fos in the paraventricular hypothalamic nucleus was performed. Body temperature was recorded continuously by telemetry through intraperitoneal transponders to analyze the LPS induced fever. The results showed that IL-1R1 KO mice displayed intact anorexia and HPA-axis activation in response to LPS, but showed attenuated but not extinguished fever. Neither the tumor necrosis factor-α (TNFα) inhibitor etanercept nor the IL-6 receptor antibody tocilizumab abolished the fever induced by LPS in IL-1R1 KO mice.

Subsequently, by using animals with cell/tissue specific deletion of IL-1R1, we examined the role of IL-1R1s in brain endothelial cells, neural cells or peripheral nerves related to IL-1R1 dependent fever. Deletion of IL-1R1 specifically in brain endothelial cells attenuated the LPS induced fever, but only during the late phase of fever, whereas deletion of IL-1R1 on neural cells or on peripheral nerves had little or no effect on the febrile response. We conclude that while IL-1 signaling is not critical for LPS induced anorexia or stress hormone release, IL-1R1, expressed on brain endothelial cells, contributes to the febrile response to LPS. However, also in the absence of IL-1R1, LPS evokes a febrile response, although this is attenuated. This remaining fever seems not to be mediated by IL-6 receptors or TNFα, but by some yet unidentified pyrogenic factor.

Reference:
Mo-P1-52
Session:
Poster Session 1 ‟Innate immunity and infection”
Presenter/s:
Takashi Matsuwaki
Presentation type:
Poster Presentation
Room:
Ishikawa Ongakudō Interchange Hall
Date:
Monday, 30 October 2017
Time:
19:10 - 21:00
Session times:
19:10 - 21:00
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