Title |
Involvement of interleukin-1 type 1 receptors in lipopolysaccharide-induced sickness responses
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Published in |
Brain, Behavior & Immunity, June 2017
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DOI | 10.1016/j.bbi.2017.06.013 |
Pubmed ID | |
Authors |
Takashi Matsuwaki, Kiseko Shionoya, Robert Ihnatko, Anna Eskilsson, Shigeru Kakuta, Sylvie Dufour, Markus Schwaninger, Ari Waisman, Werner Müller, Emmanuel Pinteaux, David Engblom, Anders Blomqvist |
Abstract |
Sickness responses to lipopolysaccharide (LPS) were examined in mice with deletion of the interleukin (IL)-1 type 1 receptor (IL-1R1). IL-1R1 knockout (KO) mice displayed intact anorexia and HPA-axis activation to intraperitoneally injected LPS (anorexia: 10 or 120 µg/kg; HPA-axis: 120 µg/kg), but showed attenuated but not extinguished fever (120 µg/kg). Brain PGE2 synthesis was attenuated, but Cox-2 induction remained intact. Neither the tumor necrosis factor-α (TNFα) inhibitor etanercept nor the IL-6 receptor antibody tocilizumab abolished the LPS induced fever in IL-1R1 KO mice. Deletion of IL-1R1 specifically in brain endothelial cells attenuated the LPS induced fever, but only during the late, 3(rd) 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. |
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Unknown | 50 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 9 | 18% |
Student > Master | 8 | 16% |
Student > Bachelor | 6 | 12% |
Professor | 5 | 10% |
Researcher | 2 | 4% |
Other | 7 | 14% |
Unknown | 13 | 26% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 6 | 12% |
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Pharmacology, Toxicology and Pharmaceutical Science | 3 | 6% |
Computer Science | 2 | 4% |
Other | 6 | 12% |
Unknown | 17 | 34% |