Back to Search
Start Over
A permethrin metabolite is associated with adaptive immune responses in Gulf War Illness
- Source :
- Brain, behavior, and immunity
- Publication Year :
- 2019
-
Abstract
- Gulf War Illness (GWI), affecting 30% of veterans from the 1991 Gulf War (GW), is a multi-symptom illness with features similar to those of patients with autoimmune diseases. The objective of the current work is to determine if exposure to GW-related pesticides, such as permethrin (PER), activates peripheral and central nervous system (CNS) adaptive immune responses. In the current study, we focused on a PER metabolite, 3-phenoxybenzoic acid (3-PBA), as this is a common metabolite previously shown to form adducts with endogenous proteins. We observed the presence of 3-PBA and 3-PBA modified lysine of protein peptides in the brain, blood and liver of pyridostigmine bromide (PB) and PER (PB + PER) exposed mice at acute and chronic post-exposure timepoints. We tested whether 3-PBA-haptenated albumin (3-PBA-albumin) can activate immune cells since it is known that chemically haptenated proteins can stimulate immune responses. We detected autoantibodies against 3-PBA-albumin in plasma from PB + PER exposed mice and veterans with GWI at chronic post-exposure timepoints. We also observed that in vitro treatment of blood with 3-PBA-albumin resulted in the activation of B- and T-helper lymphocytes and that these immune cells were also increased in blood of PB + PER exposed mice and veterans with GWI. These immune changes corresponded with elevated levels of infiltrating monocytes in the brain and blood of PB + PER exposed mice which coincided with alterations in the markers of blood-brain barrier disruption, brain macrophages and neuroinflammation. These studies suggest that pesticide exposure associated with GWI may have resulted in the activation of the peripheral and CNS adaptive immune responses, possibly contributing to an autoimmune-type phenotype in veterans with GWI.
- Subjects :
- 0301 basic medicine
Central Nervous System
Male
Metabolite
Adaptive Immunity
Inbred C57BL
Benzoates
Behavioral Neuroscience
chemistry.chemical_compound
Mice
0302 clinical medicine
Autoantibody
2.1 Biological and endogenous factors
Psychology
Persian Gulf Syndrome
Aetiology
Veterans
Brain
Middle Aged
Hapten
medicine.anatomical_structure
Female
Pyridostigmine Bromide
Adult
Central nervous system
Immunology
Article
03 medical and health sciences
Immune system
parasitic diseases
medicine
Animals
Humans
Neuroinflammation
Permethrin
Neurology & Neurosurgery
Endocrine and Autonomic Systems
business.industry
Animal
Inflammatory and immune system
Albumin
Neurosciences
Gulf War
Mice, Inbred C57BL
Pesticide
Disease Models, Animal
030104 developmental biology
chemistry
Disease Models
Gulf War Illness
business
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 08891591
- Database :
- OpenAIRE
- Journal :
- Brain, behavior, and immunity
- Accession number :
- edsair.doi.dedup.....eeb91f3794f5189c1ec1ae669cf5484e