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

Details

• Journal Article:
  Neurotoxicology
• Personal Author:
  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.
  More +
• Description:
  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.
• Subjects:
  • Animals
  • Cholinesterase Inhibitors
  • Corticosterone
  • Cytokines
  • DEET
  • Disease Models, Animal
  • Gene Expression
  • Inflammation
  • Inflammation Mediators
  • Insect Repellents
  More +
• Keywords:
  • Gulf war illness
  • Corticosterone
  • Diisopropyl fluorophosphate
  • Pyridostigmine
  • DEET
  • Inflammation
• Source:
  Neurotoxicology. 70:26-32
• DOI:
  http://dx.doi.org/10.1016/j.neuro.2018.10.006
• Pubmed ID:
  30339781
• Pubmed Central ID:
  PMC6533534
• Document Type:
  Text ; Journal Article
• Funding:
  CC999999/Intramural CDC HHSUnited States/
• Genre:
  Journal Article
• Volume:
  70
• Download URL:
  https://stacks.cdc.gov/view/cdc/79019/cdc_79019_DS1.pdf
• File Type:
  [PDF - 656.99 KB]
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:4f1582b3eed37c191ac72a668cc424450aecfee0aebfe87e7f281ff1b7802fe4d9e61b9c780bdb8447f9879f2e0dbfb6bb73d44003d347b1fcf12e1c97ac0758