title: Acute hypoxia activates the neuroimmune system, which diabetes exacerbates.
abstract: Acute hypoxia is experienced in an array of ailments and conditions, including asthma, chronic obstructive pulmonary disease, heart failure, sleep apnea, acute hypotension, and blast lung injury. Classically, infection activates the neuroimmune system, causing loss of interest in the social environment. We report that the non-infectious stimulus acute hypoxia triggers neuroimmune system activation (NSA), causing loss of interest in the social environment, and that recovery from hypoxia-induced NSA is impaired in a mouse model of type 2 diabetes. Importantly, recovery from the behavioral consequences of hypoxia-induced NSA was nearly ablated in MyD88 (myeloid differentiation factor 88) knock-out mice and in mice intracerebroventricularly administered the caspase-1 inhibitor ac-YVAD-CMK (ac-Tyr-Val-Asp-2,6-dimethylbenzoyloxymethylketone). Diabetic mice had prolonged recovery from NSA that could be halved by administration of subcutaneous interleukin-1 (IL-1) receptor antagonist (RA). These results show that acute hypoxia activates the IL-1beta arm of the neuroimmune system, which diabetes exacerbates and treatment with IL-1RA ameliorates.
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, Illinois 61801, USA.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Johnson
authors.forename: Jason C
authors.initials: JC
authors.lastname: O'Connor
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hartman
authors.forename: Richard I
authors.initials: RI
authors.lastname: Tapping
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Freund
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D002534:Hypoxia, Brain / Q000276:immunology* / Q000378:metabolism* / Q000503:physiopathology; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D015213:Neuroimmunomodulation / Q000502:physiology*; D013997:Time Factors
chemical_list: D053583:Interleukin-1beta