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

Updated November 4, 2021

November 2021
NIOSH Dataset RD-1024-2021-0

Introduction

Growing evidence suggests that Gulf War Illness (GWI) is the result of underlying neuroimmune dysfunction.  For example, previously we found that several Gulf War-relevant organophosphate, acetylcholinesterase inhibitors produce heightened neuroinflammatory responses following a sub chronic stressor exposure.  The goal of the 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. We established that our long-term GWI model produces enhanced and prolonged neuroinflammation that is dependent upon Gulf War-relevant organophosphate exposure. Propranolol treatment abrogated the neuroinflammation instigated in our model specifically, having no treatment effects in non-DFP exposed groups. Our results indicate that propranolol may be a promising therapy for GWI by treating the underlying neuroinflammation associated with Gulf War-relevant physiological stress and organophosphate exposures.

Data Collection 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.

Publications using this dataset

Michalovicz LT, Kelly KA, Miller DB, Sullivan K, O’Callaghan JP (2021) The β-adrenergic receptor blocker and anti-inflammatory drug propranolol mitigates brain cytokine expression in a long-term model of Gulf War Illness. Life Sciences 285: 119962. DOI: 10.1016/j.lfs.2021.119962.

Acknowledgements

The work that generated this dataset was supported by Intramural funding from the Centers for Disease Control and Prevention – National Institute for Occupational Safety and Health and a Congressionally-Directed Medical Research Program, Gulf War Illness Research Program grant (GW120037) for the Boston University Gulf War Illness Consortium (K. Sullivan, PI).

When a publication makes use of this dataset, acknowledgement of the development of the dataset should be attributed to Michalovicz LT, Kelly KA, Miller DB, Sullivan K, O’Callaghan JP.

Contact

For further information contact:

NIOSH/HELD Toxicology and Molecular Biology Branch
(304) 285-6272

Page last reviewed: November 4, 2021