Abstract
BACKGROUND: The extensive use of insecticides in modern agriculture has raised concerns about potential chronic effects on human health beyond acute toxicity. Limited evidence exists regarding their impact on immune regulation and intestinal barrier integrity, two key components of host-environment interactions. METHODS: Human in-vitro models were used to investigate the immunomodulatory and intestinal effects of several commonly used agricultural insecticides. Primary human macrophages derived from peripheral blood mononuclear cells were exposed to insecticides to assess cell viability and polarization status. Intestinal barrier function was evaluated using Caco-2 cell monolayers by measuring oxidative stress, epithelial integrity, paracellular permeability, and tight junction organization. RESULTS: The tested insecticides induced a pro-inflammatory macrophage phenotype, characterized by increased expression of M1 markers and reduced M2 markers, without affecting cell viability. In Caco-2 cells, insecticide exposure compromised epithelial barrier integrity and disrupted tight junction organization. In this context, neither Spinetoram nor Spirotetramat induced notable oxidative stress under pro-oxidant conditions. However, Spirotetramat caused a significant increase in paracellular permeability. CONCLUSIONS: These findings indicate that commonly used insecticides can modulate immune responses and impair intestinal barrier function, suggesting potential mechanisms by which chronic low-level exposure may contribute to immune dysregulation and epithelial dysfunction in humans.