The β-adrenergic receptor blocker and anti-inflammatory drug propranolol mitigates brain cytokine expression in a long-term model of Gulf War Illness

Details

• Alternative Title:
  Life Sci
• Personal Author:
  Michalovicz, Lindsay T. ; Kelly, Kimberly A. ; Miller, Diane B. ; Sullivan, Kimberly ; O’Callaghan, James P.
• Description:
  Aims:
  
  Growing evidence suggests that Gulf War Illness (GWI) is the result of underlying neuroimmune dysfunction. For example, previously we found that several GWI-relevant organophosphate acetylcholinesterase inhibitors produce heightened neuroinflammatory responses following subchronic exposure to stress hormone as a mimic of high physiological stress. The goal of the current study was to evaluate the potential for the β-adrenergic receptor inhibitor and anti-inflammatory drug, propranolol, to treat neuroinflammation in a novel long-term mouse model of GWI.
  
  Main methods:
  
  Adult male C57BL/6J mice received a subchronic exposure to corticosterone (CORT) at levels mimicking high physiological stress followed by exposure to the sarin surrogate, diisopropyl fluorophosphate (DFP). These mice were then re-exposed to CORT every other week for a total of five weeks, followed by a systemic immune challenge with lipopolysaccharide (LPS). Animals receiving the propranolol treatment were given a single dose (20 mg/kg, i.p.) either four or 11 days prior to the LPS challenge. The potential anti-neuroinflammatory effects of propranolol were interrogated by analysis of cytokine mRNA expression.
  
  Key findings:
  
  We found that our long-term GWI model produces a primed neuroinflammatory response to subsequent immune challenge that is dependent upon GWI-relevant organophosphate exposure. Propranolol treatment abrogated the elaboration of inflammatory cytokine mRNA expression in the brain instigated in our model, having no treatment effects in non-DFP exposed groups.
  
  Significance:
  
  Our results indicate that propranolol may be a promising therapy for GWI with the potential to treat the underlying neuroinflammation associated with the illness.
  
  
• Subjects:
  Adrenergic Beta-Antagonists Animals Anti-Inflammatory Agents, Non-Steroidal Article Brain Corticosterone Cytokines Diisopropyl Fluorophosphate Disease Models, Animal Encephalitis Gulf War Illness Male Mice Mice, Inbred C57BL Neuroinflammation Persian Gulf Syndrome Propranolol Treatment

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• Source:
  Life Sci. 285:119962
• Pubmed ID:
  34563566
• Pubmed Central ID:
  PMC9047058
• Document Type:
  Journal Article
• Funding:
  CC999999/ImCDC/Intramural CDC HHSUnited States/
• Volume:
  285
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:e289ac581d62c7cdc789b4541e0b1df4e733aa59f889ea7f42eb7ad7c4152ed7
• Download URL:
  https://stacks.cdc.gov/view/cdc/116875/cdc_116875_DS1.pdf
• File Type:
  [PDF - 712.14 KB ]