title: Pyridostigmine bromide (PYR) alters immune function in B6C3F1 mice.
abstract: Pyridostigmine bromide (PYR) is an anticholinesterase drug indicated for the treatment of myasthenia gravis and neuromuscular blockade reversal. It acts as a reversible cholinesterase inhibitor and was used as a pretreatment for soldiers during Operation Desert Storm to protect against possible nerve gas attacks. Since that time, PYR has been implicated as a possible causative agent contributing to Gulf War Illness. PYR's mechanism of action has been well-delineated with regards to its effects on the nervous system, yet little is known regarding potential effects on immunological function. To evaluate the effects of PYR on immunological function, adult female B6C3F1 mice were gavaged daily for 14 days with PYR (0, 1, 5, 10, or 20 mg/kg/day). Immune parameters assessed were lymphoproliferation, natural killer cell activity, the SRBC-specific antibody plaque-forming cell (PFC) response, thymus and spleen weight and cellularity, and thymic and splenic CD4/CD8 lymphocyte subpopulations. Exposure to PYR did not alter splenic and thymus weight or splenic cellularity. However, 20 mg PYR/kg/day decreased thymic cellularity with decreases in both CD4+/CD8+ (20 mg/kg/day) and CD4-/CD8- (10 and 20 mg/kg/day) cell types. Functional immune assays indicated that lymphocyte proliferative responses and natural killer cell activity were normal; whereas exposure to PYR significantly decreased primary IgM antibody responses to a T-cell dependent antigen at the 1, 5, 10 and 20 mg/kg treatment levels for 14 days. This is the first study to examine the immunotoxicological effects of PYR and demonstrate that this compound selectively suppresses humoral antibody responses.
authors.affiliation: Department of Rheumatology and Immunology, Medical University of South Carolina, Charleston, South Carolina 29412, USA. pedenada@musc.edu
authors.forename: M M
authors.initials: MM
authors.lastname: Peden-Adams
authors.forename: A C
authors.initials: AC
authors.lastname: Dudley
authors.forename: J G
authors.initials: JG
authors.lastname: EuDaly
authors.forename: C T
authors.initials: CT
authors.lastname: Allen
authors.forename: G S
authors.initials: GS
authors.lastname: Gilkeson
authors.forename: D E
authors.initials: DE
authors.lastname: Keil
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D002452:Cell Count; D003208:Concanavalin A / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D007109:Immunity / Q000187:drug effects* / Q000276:immunology; D007111:Immunity, Cellular / Q000187:drug effects; D007694:Killer Cells, Natural / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D011729:Pyridostigmine Bromide / Q000008:administration & dosage / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000254:growth & development; D014611:Vaccination
chemical_list: D008070:Lipopolysaccharides; D000072317:Polychlorinated Dibenzodioxins; C440499:lipopolysaccharide, Escherichia coli O111 B4; D003208:Concanavalin A; D003907:Dexamethasone; D011729:Pyridostigmine Bromide