6533b7d1fe1ef96bd125c3f5

RESEARCH PRODUCT

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

Robert IhnatkoWerner MüllerTakashi MatsuwakiAri WaismanMarkus SchwaningerEmmanuel PinteauxAnders BlomqvistAnna EskilssonDavid EngblomShigeru KakutaSylvie DufourKiseko Shionoya

subject

0301 basic medicineLipopolysaccharidesMalemedicine.medical_specialtyLipopolysaccharideFeverCell- och molekylärbiologiImmunologyHypothalamusAnorexiaEtanerceptInterleukin-1 type 1 receptor; Lipopolysaccharide; Fever; Anorexia; ACTH; Corticosterone; Endothelial cells; THF alpha; Interleukin-6; PGE(2)03 medical and health sciencesBehavioral Neurosciencechemistry.chemical_compoundEating0302 clinical medicineAdrenocorticotropic HormoneCorticosteroneInternal medicinemedicineJournal ArticleAnimalsInterleukin 6ReceptorIllness BehaviorInflammationMice KnockoutReceptors Interleukin-1 Type IbiologyEndocrine and Autonomic Systemsbusiness.industryInterleukinBrainEndothelial CellsAnorexia030104 developmental biologyEndocrinologychemistrybiology.proteinTumor necrosis factor alphaFemalemedicine.symptomInflammation MediatorsbusinessCorticosterone030217 neurology & neurosurgeryCell and Molecular Biologymedicine.drug

description

Sickness responses to lipopolysaccharide (LPS) were examined in mice with deletion of the interleukin (IL)-1 type 1 receptor (IL-1R1). IL-1R1 knockout (1(0) mice displayed intact anorexia and HPA-axis activation to intraperitoneally injected LPS (anorexia: 10 or 120 mu g/kg; HPA-axis: 120 mu g/kg), but showed attenuated but not extinguished fever (120 g/kg). Brain PGE2 synthesis was attenuated, but Cox-2 induction remained intact. Neither the tumor necrosis factor-alpha (TNF alpha) 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 TNFa, but by some yet unidentified pyrogenic factor.  Funding Agencies|Japan Society for the Promotion of Science [15K18800]; Swedish Research Council [20725, 07879]; Knut and Alice Wallenberg foundation; Swedish Brain Foundation; Swedish Cancer Foundation [213/692]; County Council of Ostergotland; Sixth Research Framework Programme of the European Union, Project MUGEN [MUGEN LSHG-CT-2005-005203]; MRC research grant [G0801296]

yearjournalcountryeditionlanguage
2017-01-01
10.1016/j.bbi.2017.06.013https://doi.org/10.1016/j.bbi.2017.06.013