Involvement of interleukin-1 type 1 receptors in lipopolysaccharide-induced sickness responses

Takashi Matsuwaki, Kiseko Shionoya, Robert Ihnatko, Anna Eskilsson, Shigeru Kakuta, Sylvie Dufour, Markus Schwaninger, Ari Waisman, Werner Müller, Emmanuel Pinteaux, David Engblom, Anders Blomqvist*

*Corresponding author for this work
2 Citations (Scopus)


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, 3rd 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.

Original languageEnglish
JournalBrain, Behavior, and Immunity
Pages (from-to)165-176
Number of pages12
Publication statusPublished - 01.11.2017

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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