title: Chlorisondamine, a sympathetic ganglionic blocker, moderates the effects of whole-body irradiation (WBI) on early host defense to a live bacterial challenge.
abstract: There is a growing consensus that long-term deficits in the brain are due to dynamic interactions between multiple neural and immune cell types. Specifically, radiation induces an inflammatory response, including changes in neuromodulatory pro- and anti-inflammatory cytokine secretion. The purpose of this study was to establish that there is sympathetic involvement in radiation-induced decrements early in in vivo immune function host defense. Female, 8-9 week-old C57BL/6J mice were exposed to whole-body irradiation (WBI). There were 8 groups with radiation (0 vs. 3 Gy protons), immune challenge (Escherichia coli) and exposure to the sympathetic ganglionic blocker, chlorisondamine (1 mg/kg weight, i.p.), as independent variables. Ten days post-irradiation, mice were inoculated with E. coli intraperitoneally and sacrificed 90-120 min later. The data suggest that radiation-induced changes in immune function may in part be mediated by the sympathetic nervous system. Briefly, we found that radiation augments the bacteria-induced inflammatory cytokine response, particularly those cytokines involved in innate immunity. However, this augmentation can be reduced by the ganglionic blockade.
authors.affiliation: Department of Basic Sciences, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States; Division of Radiation Research, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States; Division of Biochemistry and Microbiology, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States. Electronic address: mpecaut@llu.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Pecaut
authors.affiliation: Department of Basic Sciences, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States.
authors.forename: Shalini
authors.initials: S
authors.lastname: Mehrotra
authors.affiliation: Division of Trauma Services, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States.
authors.forename: Xian
authors.initials: X
authors.lastname: Luo-Owen
authors.affiliation: Department of Basic Sciences, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States.
authors.forename: Erben J M
authors.initials: EJ
authors.lastname: Bayeta
authors.affiliation: Department of Pathology and Human Anatomy, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States.
authors.forename: Denise L
authors.initials: DL
authors.lastname: Bellinger
authors.affiliation: Department of Basic Sciences, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States; Division of Radiation Research, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States; Division of Biochemistry and Microbiology, Loma Linda University and Medical Center, Loma Linda, 92354 CA, United States.
authors.forename: Daila S
authors.initials: DS
authors.lastname: Gridley
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology*; D001424:Bacterial Infections / Q000276:immunology* / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D002714:Chlorisondamine / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000276:immunology; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology*; D054884:Host-Pathogen Interactions / Q000187:drug effects* / Q000276:immunology*; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010587:Phagocytosis / Q000276:immunology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014916:Whole-Body Irradiation
chemical_list: D002395:Catecholamines; D016207:Cytokines; D005730:Ganglionic Blockers; D017382:Reactive Oxygen Species; D002714:Chlorisondamine
keywords: Chlorisondamine; Cytokines; Protons; Sympathetic nervous system; Whole-body irradiation