{"doi":"10.1016/j.lfs.2021.119962","title":"The β-adrenergic receptor blocker and anti-inflammatory drug propranolol mitigates brain cytokine expression in a long-term model of Gulf War Illness","abstract":"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.","journal":"Life Sciences","year":2021,"id":181503,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9613,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":318257,"name":"Kimberly A. Kelly","orcid":"0000-0002-1146-3137","position":1,"is_corresponding":false},{"id":510390,"name":"Diane B. Miller","orcid":"0000-0002-7899-3490","position":2,"is_corresponding":false},{"id":270294,"name":"Kimberly Sullivan","orcid":"0000-0001-7940-6123","position":3,"is_corresponding":false},{"id":318258,"name":"James P. O’Callaghan","orcid":"0000-0001-8497-4598","position":4,"is_corresponding":false},{"id":319433,"name":"Lindsay T. Michalovicz","orcid":null,"position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-18T23:48:05.146883Z","pmid":"34563566","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}