title: Euflammation attenuates peripheral inflammation-induced neuroinflammation and mitigates immune-to-brain signaling.
abstract: Peripheral inflammation can trigger a number of neuroinflammatory events in the CNS, such as activation of microglia and increases of proinflammatory cytokines. We have previously identified an interesting phenomenon, termed "euflammation", which can be induced by repeated subthreshold infectious challenges. Euflammation causes innate immune alterations without overt neuroimmune activation. In the current study, we examined the protective effect of euflammation against peripheral inflammation-induced neuroinflammation and the underlying mechanisms. When Escherichia coli or lipopolysaccharide (LPS) was injected inside or outside the euflammation induction locus (EIL), sickness behavior, global microglial activation, proinflammatory cytokine production in the brain, expression of endothelial cyclooxygenase II and induction of c-fos expression in the paraventricular nucleus of the hypothalamus were all attenuated in the euflammatory mice compared with those in the control unprimed mice. Euflammation also modulated innate immunity outside the EIL by upregulating receptors for pathogen-associated molecular patterns in spleen cells. In addition, euflammation attenuated CNS activation in response to an intra-airpouch (outside the EIL) injection of LPS without suppressing the cytokine expression in the airpouch. Collectively, our study demonstrates that signaling of peripheral inflammation to the CNS is modulated dynamically by peripheral inflammatory kinetics. Specifically, euflammation can offer effective protection against both bacterial infection and endotoxin induced neuroinflammation.
authors.affiliation: Division of Biosciences, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA; Department of Neuroscience, CNR Behavior Core, Tufts University, Arnold Building, 116 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Division of Biosciences, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Nemeth
authors.affiliation: Department of Neuroscience, CNR Behavior Core, Tufts University, Arnold Building, 116 Harrison Avenue, Boston, MA 02111, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tarr
authors.affiliation: Division of Biosciences, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Natalya
authors.initials: N
authors.lastname: Belevych
authors.affiliation: Division of Biosciences, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Zunera W
authors.initials: ZW
authors.lastname: Syed
authors.affiliation: Division of Biosciences, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Yufen
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Ahmad S
authors.initials: AS
authors.lastname: Ismail
authors.affiliation: Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Nathaniel S
authors.initials: NS
authors.lastname: Reed
authors.affiliation: Division of Biosciences, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: John F
authors.initials: JF
authors.lastname: Sheridan
authors.affiliation: Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Akul R
authors.initials: AR
authors.lastname: Yajnik
authors.affiliation: Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Damon J
authors.initials: DJ
authors.lastname: Disabato
authors.affiliation: Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Division of Biosciences, The Ohio State University, 305 W. 12th Ave, Columbus, OH 43210, USA; Institute for Behavioral Medicine Research, The Ohio State University Wexner Medical Center, 460 Medical Center Dr., Columbus, OH 43210, USA. Electronic address: quan.14@osu.edu.
authors.forename: Ning
authors.initials: N
authors.lastname: Quan
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004731:Endotoxins / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D017628:Microglia / Q000378:metabolism; D015213:Neuroimmunomodulation / Q000276:immunology*; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism
chemical_list: D016207:Cytokines; D004731:Endotoxins; D008070:Lipopolysaccharides
keywords: Cytokines; Lipopolysaccharide; Microglia; Neuroimmune
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