TY - JOUR
T1 - Involvement of interleukin-1 type 1 receptors in lipopolysaccharide-induced sickness responses
AU - Matsuwaki, Takashi
AU - Shionoya, Kiseko
AU - Ihnatko, Robert
AU - Eskilsson, Anna
AU - Kakuta, Shigeru
AU - Dufour, Sylvie
AU - Schwaninger, Markus
AU - Waisman, Ari
AU - Müller, Werner
AU - Pinteaux, Emmanuel
AU - Engblom, David
AU - Blomqvist, Anders
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85021692843&partnerID=8YFLogxK
U2 - 10.1016/j.bbi.2017.06.013
DO - 10.1016/j.bbi.2017.06.013
M3 - Journal articles
C2 - 28655587
AN - SCOPUS:85021692843
SN - 0889-1591
VL - 66
SP - 165
EP - 176
JO - Brain, Behavior, and Immunity
JF - Brain, Behavior, and Immunity
ER -