Corticosterone and pyridostigmine/DEET exposure attenuate peripheral cytokine expression: Supporting a dominant role for neuroinflammation in a mouse model of Gulf War Illness

Lindsay T. Michalovicz, Alicia R. Locker, Kimberly A. Kelly, Julie V. Miller, Zachary Barnes, Mary Ann Fletcher, Diane B. Miller, Nancy G. Klimas, Mariana Morris, Stephen M. Lasley, James P. O'Callaghan

    Research output: Contribution to journalArticle

    Abstract

    Gulf War Illness (GWI) is a chronic multi-symptom disorder experienced by as many as a third of the veterans of the 1991 Gulf War; the constellation of “sickness behavior” symptoms observed in ill veterans is suggestive of a neuroimmune involvement. Various chemical exposures and conditions in theater have been implicated in the etiology of the illness. Previously, we found that GW-related organophosphates (OPs), such as the sarin surrogate, DFP, and chlorpyrifos, cause neuroinflammation. The combination of these exposures with exogenous corticosterone (CORT), mimicking high physiological stress, exacerbates the observed neuroinflammation. The potential relationship between the effects of OPs and CORT on the brain versus inflammation in the periphery has not been explored. Here, using our established GWI mouse model, we investigated the effects of CORT and DFP exposure, with or without a chronic application of pyridostigmine bromide (PB) and N,N-diethyl-meta-toluamide (DEET), on cytokines in the liver and serum. While CORT primed DFP-induced neuroinflammation, this effect was largely absent in the periphery. Moreover, the changes found in the peripheral tissues do not correlate with the previously reported neuroinflammation. These results not only support GWI as a neuroimmune disorder, but also highlight the separation between central and peripheral effects of these exposures.

    LanguageEnglish (US)
    Pages26-32
    Number of pages7
    JournalNeuroToxicology
    Volume70
    DOIs
    StatePublished - Jan 1 2019

    Fingerprint

    DEET
    Gulf War
    Pyridostigmine Bromide
    Corticosterone
    Isoflurophate
    Cytokines
    Inflammation
    Organophosphates
    Veterans
    Sarin
    Illness Behavior
    Chlorpyrifos
    Physiological Stress
    Theaters
    Encephalitis
    Liver
    Brain
    Tissue
    Serum

    Keywords

    • Corticosterone
    • DEET
    • Diisopropyl fluorophosphate
    • Gulf war illness
    • Inflammation
    • Pyridostigmine

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Toxicology

    Cite this

    Corticosterone and pyridostigmine/DEET exposure attenuate peripheral cytokine expression : Supporting a dominant role for neuroinflammation in a mouse model of Gulf War Illness. / Michalovicz, Lindsay T.; Locker, Alicia R.; Kelly, Kimberly A.; Miller, Julie V.; Barnes, Zachary; Fletcher, Mary Ann; Miller, Diane B.; Klimas, Nancy G.; Morris, Mariana; Lasley, Stephen M.; O'Callaghan, James P.

    In: NeuroToxicology, Vol. 70, 01.01.2019, p. 26-32.

    Research output: Contribution to journalArticle

    Michalovicz, Lindsay T. ; Locker, Alicia R. ; Kelly, Kimberly A. ; Miller, Julie V. ; Barnes, Zachary ; Fletcher, Mary Ann ; Miller, Diane B. ; Klimas, Nancy G. ; Morris, Mariana ; Lasley, Stephen M. ; O'Callaghan, James P. / Corticosterone and pyridostigmine/DEET exposure attenuate peripheral cytokine expression : Supporting a dominant role for neuroinflammation in a mouse model of Gulf War Illness. In: NeuroToxicology. 2019 ; Vol. 70. pp. 26-32.
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