The Β-Adrenergic Receptor Blocker and Anti-Inflammatory Drug Propranolol Mitigates Brain Cytokine Expression in a Long-Term Model of Gulf War Illness

Details

• Personal Author:
  Kellly KA ; Michalovicz LT ; Miller DB ; O'Callaghan JP ; Sullivan K
• 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. [Description provided by NIOSH]
• Subjects:
  Animals Endocrine System Immune System Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Acetylcholinesterase Animal Studies Author Keywords: Gulf War Illness Corticosterone Cytokines Diisopropyl Fluorophosphate Hormones Immune Reaction Military Personnel Neuroinflammation Neurological Disorders Physiological Stress Propranolol Psychosocial Factors Sarin Treatment

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• ISSN:
  0024-3205
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1 ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  285
• NIOSHTIC Number:
  nn:20063715
• Citation:
  Life Sci 2021 Nov; 285:119962
• Contact Point Address:
  James P. O'Callaghan, a Health Effects Laboratory Division, Centers for Disease Control and Prevention-National Institute for Occupational Safety and Health, Morgantown, WV
• Email:
  Jdo5@cdc.gov
• CAS Registry Number:
  Diisopropyl fluorophosphate (CAS RN 55-91-4) ; Propranolol (CAS RN 525-66-6) ; Sarin (CAS RN 107-44-8)
• Federal Fiscal Year:
  2022
• Peer Reviewed:
  True
• Source Full Name:
  Life Sciences
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:5e0a21923a790bc21915b4d9e6637bfc0ae55c272be0cea17f731c1962330b378725456865115b9e7e80f9bcb8e71a4d8dd41697c3258e9251c6c63949ec9fbf
• Download URL:
  https://stacks.cdc.gov/view/cdc/222276/cdc_222276_DS1.pdf
• File Type:
  [PDF - 1.41 MB ]