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

Research output: Contribution to journalArticle

  • External authors:
  • Takashi Matsuwaki
  • Kiseko Shionoya
  • Robert Ihnatko
  • Anna Eskilsson
  • Shigeru Kakuta
  • Sylvie Dufour
  • Markus Schwaninger
  • Ari Waisman
  • David Engblom
  • Anders Blomqvist


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 120µg/kg; HPA-axis: 120µg/kg), but showed attenuated but not extinguished fever (120µg/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.

Bibliographical metadata

Original languageEnglish
JournalBrain, Behavior, and Immunity
Early online date24 Jun 2017
Publication statusPublished - 2017