title: The inhalation anesthetic isoflurane increases levels of proinflammatory TNF-α, IL-6, and IL-1β.
abstract: Anesthetics have been reported to promote Alzheimer's disease (AD) neuropathogenesis by inducing β-amyloid protein accumulation and apoptosis. Neuroinflammation is associated with the emergence of AD. We therefore set out to determine the effects of the common anesthetic isoflurane on the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β, the proinflammatory cytokines, in vitro and in vivo, employing Western blot, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and reverse transcriptase polymerase chain reaction (RT-PCR). Here, we show that a clinically relevant isoflurane anesthesia increased the protein and messenger ribonucleic acid (mRNA) levels of TNF-α, IL-6, and IL-1β in the brain tissues of mice. The isoflurane anesthesia increased the amounts of TNF-α immunostaining positive cells in the brain tissues of mice, the majority of which were neurons. Furthermore, isoflurane increased TNF-α levels in primary neurons, but not microglia cells, of mice. Finally, isoflurane induced a greater degree of TNF-α increase in the AD transgenic mice than in the wild-type mice. These results suggest that isoflurane may increase the levels of proinflammatory cytokines, which may cause neuroinflammation, leading to promotion of AD neuropathogenesis.
authors.affiliation: Geriatric Anesthesia Research Unit, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129-2060, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Yuanlin
authors.initials: Y
authors.lastname: Dong
authors.forename: Guohua
authors.initials: G
authors.lastname: Zhang
authors.forename: Yiying
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Culley
authors.forename: Gregory
authors.initials: G
authors.lastname: Crosby
authors.forename: Edward R
authors.initials: ER
authors.lastname: Marcantonio
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: Zhongcong
authors.initials: Z
authors.lastname: Xie
mesh_terms: D000280:Administration, Inhalation; D018685:Anesthetics, Inhalation; D000818:Animals; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011897:Random Allocation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D015854:Up-Regulation / Q000502:physiology
chemical_list: D018685:Anesthetics, Inhalation; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007530:Isoflurane