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
NIOSH Dataset RD-1024-2021-0
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.
- GWI GFAP Protein excel icon[XLS – 344 B]
- GWI PCR Cortex excel icon[XLS – 1 KB]
- GWI PCR Hippocampus excel icon[XLS – 1 KB]
- GWI Propranolol PCR Cortex excel icon[XLS – 2 KB]
- GWI Propranolol PCR Hippocampus excel icon[XLS – 2 KB]
- GWI pSTAT3 Protein excel icon[XLS – 365 B]
- Data Dictionary pdf icon[PDF – 52 KB]
- Methods pdf icon[PDF – 67 KB]
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.
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.
For further information contact:
NIOSH/HELD Toxicology and Molecular Biology Branch