title: Increased cytokine and chemokine gene expression in the CNS of mice during heat stroke recovery.
abstract: Heat stroke (HS) is characterized by a systemic inflammatory response syndrome (SIRS) consisting of profound core temperature (Tc) changes in mice. Encephalopathy is common at HS collapse, but inflammatory changes occurring in the brain during the SIRS remain unidentified. We determined the association between inflammatory gene expression changes in the brain with Tc disturbances during HS recovery in mice. Gene expression changes of heat shock protein (HSP)72, heme oxygenase (hmox1), cytokines (IL-1β, IL-6, TNF-α), cyclooxygenase enzymes (COX-1, COX-2), chemokines (MCP-1, MIP-1α, MIP-1β, CX3CR1), and glia activation markers (CD14, aif1, vimentin) were examined in the hypothalamus (HY) and hippocampus (HC) of control (Tc ∼ 36.0°C) and HS mice at Tc,Max (42.7°C), hypothermia depth (HD; 29.3 ± 0.4°C), and fever (37.8 ± 0.3°C). HSP72 (HY<HC) and IL-1β (HY only) were the only genes that showed increased expression at Tc,Max. HSP72 (HY < HC), hmox1 (HY < HC), cytokine (HY = HC), and chemokine (HY = HC) expression was highest at HD and similar to controls during fever. COX-1 expression was unaffected by HS, whereas HD was associated with approximately threefold increase in COX-2 expression (HY only). COX-2 expression was not increased during fever and indomethacin (COX inhibitor) had no effect on this Tc response indicating fever is regulated by other inflammatory pathways. CD14, aif1, and vimentin activation at HD coincided with maximal cytokine and chemokine expression suggesting glia cells are a possible source of brain cytokines and chemokines during HS recovery. The inflammatory gene expression changes during HS recovery suggest cytokines and/or chemokines may be initiating development or rewarming from hypothermia, whereas fever pathway(s) remain to be elucidated.
authors.affiliation: United State Army Research Institute of Environmental Medicine, Military Nutrition Division.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Biedenkapp
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Leon
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001833:Body Temperature Regulation; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005334:Fever / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018883:Heat Stroke / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D006360:Heat-Shock Proteins / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism; D020127:Recovery of Function; D015398:Signal Transduction; D018746:Systemic Inflammatory Response Syndrome / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D018925:Chemokines; D016861:Cyclooxygenase Inhibitors; D016207:Cytokines; D006360:Heat-Shock Proteins; D018836:Inflammation Mediators; D008565:Membrane Proteins; C077623:Ptgs2 protein, mouse; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496512:Ptgs1 protein, mouse
keywords: chemokines; cytokines; fever; heat stroke; hypothermia; systemic inflammatory response