Georgia Southern Examines Immunomodulating Effects of Bacterial Endotoxin
How very high exposure levels to bacterial endotoxin in a farming environment provide protection against respiratory allergic symptoms and low-to-moderate levels of endotoxin in urban homes promote allergic response is unclear. Dose-specific bacterial endotoxin or LPS-induced tolerance mechanisms can affect lung inflammations, coupled with the Th2 immune responses. In this research study, the authors explored the effects of intranasal exposure of endotoxin at two different doses (based on occupational exposure levels during handling of agricultural wastes) in OVA-sensitized allergic wild type (WT) and TLR4-KO mice, particularly, with respect to Th2 cytokines and Tregs level. Low-dose endotoxin (100 ng) exposure prohibited airway tolerance and failed to generate T-cell-dependent protection against lung inflammations in allergic mice. Furthermore, low Tregs at the inflammatory site and induced Th2 cytokines, as well as IL-6 and IL-25, suggested that low-dose might be associated with the suppression of tolerance mechanisms. In contrast, high-dose endotoxin (20 µg) favored the suppression of Th2 cytokines, IL-6 and IL-25, but failed to induce Th1 cytokines (e.g. IFN-γ). The results suggest that low-dose LPS can enhance airway allergic inflammation through failing of antigen-dependent immune regulatory homeostasis. The study concludes that exposure levels of endotoxin can determine the generation of inflammatory responses in respiratory allergy.
“Dose-dependent immunomodulating effects of endotoxin in allergic airway inflammation,” was recently published in Innate Immunity.
Dr. Sudhir Kumar, Department of Pediatrics at the Cincinnati Children’s Hospital Medical Center was the lead author and Dr. Atin Adhikari, assistant professor of environmental health sciences at the Jiann-Ping Hsu College of Public Health was the co-author.