Maddalon Ambra, Galbiati Valentina, Ferrian Melissa, Mastrangelo Giuseppe, Meroni Simone, Dioni Laura, Mandić-Rajčević Stefan, Colosio Claudio, Corsini Emanuela, Porru Stefano
Laboratory of Toxicology, Department of Pharmacological and Biomolecular Sciences "Rodolfo Paoletti", Università Degli Studi di Milano, Via Balzaretti 9, 20133, Milan, Italy.
Section of Occupational Medicine, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.
Arch Toxicol. 2025 Sep 8. doi: 10.1007/s00204-025-04156-3.
Glyphosate, a widely used herbicide, has raised concerns regarding its impact on human health and the environment due to its widespread and excessive use. Adverse effects on the immune system have been reported. In this study, 26 vineyard workers in Veneto vineyards were examined before and after glyphosate applications to investigate possible immune parameter changes. Glyphosate exposure led to alterations in plasma cytokine levels, including marked increases in IL-4 and IL-5, a modest rise in IFN-γ, and a decrease in IL-8. No changes in plasma IL-12/23p40, IL17 and IL-33 were found. The IFN-γ/IL-4 ratio decreased, accompanied by changes in T cell subpopulations. Notably, a decrease in the T helper 1/T helper 2 cell ratio, attributed to reduced Th1 cells and increased Th2 cells, was observed, aligning with the elevated Th2 cytokines. A reduction in plasmatic extracellular vesicular miR-500a levels following glyphosate exposure was found, potentially contributing to the immunological findings. A slight decrease in plasma lipopolysaccharide levels in exposed workers excluded systemic inflammation from increased intestinal permeability but hinted at a possible association with glyphosate-induced microbiota dysbiosis. Since the shikimate pathway, targeted by glyphosate, is also present in Gram-negative bacteria. Overall, these findings suggest that glyphosate can affect the immune system, favoring Th2 responses. While more research is needed to establish causality with the association of glyphosate exposure with the development of allergic reactions in susceptible individuals, our results shed light on potential underlying mechanisms.
草甘膦是一种广泛使用的除草剂，由于其广泛且过量使用，已引发对其对人类健康和环境影响的担忧。已有关于其对免疫系统产生不良影响的报道。在本研究中，对威尼托葡萄园的26名葡萄园工人在草甘膦施用前后进行了检查，以调查免疫参数可能发生的变化。草甘膦暴露导致血浆细胞因子水平发生改变，包括白细胞介素-4（IL-4）和白细胞介素-5（IL-5）显著升高、干扰素-γ（IFN-γ）适度上升以及白细胞介素-8（IL-8）下降。未发现血浆白细胞介素-12/23 p40、白细胞介素-17和白细胞介素-33有变化。IFN-γ/IL-4比值下降，同时T细胞亚群发生变化。值得注意的是，观察到辅助性T细胞1/辅助性T细胞2（Th1/Th2）细胞比值下降，这归因于Th1细胞减少和Th2细胞增加，与Th2细胞因子升高一致。发现草甘膦暴露后血浆细胞外囊泡微小RNA-500a（miR-500a）水平降低，这可能是导致免疫结果的原因。暴露工人的血浆脂多糖水平略有下降，排除了肠道通透性增加导致的全身炎症，但暗示可能与草甘膦诱导的微生物群失调有关。由于草甘膦靶向的莽草酸途径也存在于革兰氏阴性细菌中。总体而言，这些发现表明草甘膦可影响免疫系统，促进Th2反应。虽然需要更多研究来确定草甘膦暴露与易感个体过敏反应发生之间的因果关系，但我们的结果揭示了潜在机制。
