La respuesta sistémica Th17/IL-17A aparece antes del proceso neurodegenerativo en el hipocampo de ratas expuestas a bajas dosis de ozono

Abstract

IntroductionExposure to low doses of O3 leads to a state of oxidative stress. Some studies show that oxidative stress can modulate both the CNS and systemic inflammation, which are important factors in the development of Alzheimer disease (AD). ObjectiveThis study aims to evaluate changes in the frequency of Th17-like cells (CD3+CD4+IL-17A+), the concentration of IL-17A in peripheral blood, and hippocampal immunoreactivity to IL-17A in rats exposed to low doses of O3. MethodsOne hundred eight male Wistar rats were randomly assigned to 6 groups (n=18) receiving the following treatments: control (O3 free) or O3 exposure (0.25ppm, 4hours daily) over 7, 15, 30, 60, and 90 days. Twelve animals from each group were decapitated and a peripheral blood sample was taken to isolate plasma and mononuclear cells. Plasma IL-17A was quantified using LUMINEX, while Th17-like cells were counted using flow cytometry. The remaining 6 rats were deeply anaesthetised and underwent transcardial perfusion for immunohistological study of the hippocampus. ResultsResults show that exposure to O3 over 7 days resulted in a significant increase in the frequency of Th17-like cells and levels of IL-17A in peripheral blood. However, levels of Th17/IL-17A in peripheral blood were lower at day 15 of exposure. We also observed increased IL-17A in the hippocampus beginning at 30 days of exposure. ConclusionThese results indicate that O3 induces a short-term, systemic Th17-like/IL-17A effect and an increase of IL-17A in the hippocampal tissue during the chronic neurodegenerative process.