Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, West Wing. 5F 3-1-1, Maidashi, Higashi-ku, Fukuoka, Japan; Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki-shi, Nagasaki, Japan.
Gunge Hospital, 1-9, Suehiro, Goto-shi, Nagasaki, Japan; Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, Nagasaki-shi, Nagasaki, Japan.
Environ Res. 2020 Jun;185:109415. doi: 10.1016/j.envres.2020.109415. Epub 2020 Mar 21.
In 1968 in western Japan, polychlorinated biphenyl-contaminated "Kanemi rice oil" was used in cooking, causing food poisoning in many people. More than 50 years have passed since the Yusho incident, and although inflammatory disorders such as suppuration have been observed in Yusho patients, the etiology of this inflammation susceptibility remains obscure.
To investigate the mechanisms of susceptibility to inflammation in Yusho patients, peripheral immune cell fractions and concentrations of inflammatory cytokines were evaluated in blood samples collected from both Yusho patients and age-matched healthy subjects undergoing medical examination in Nagasaki.
To exclude diagnostic uncertainty, serum levels of polychlorinated biphenyl (PCB), polychlorinated quarterphenyl (PCQ), and polychlorinated dibenzofuran (PCDF) were measured. Immune cell (e.g. natural killer and regulatory T cell) populations were analyzed by flow cytometry. Serum cytokines involved in immune cell activation were measured by ELISA.
The relative proportion of natural killer cells was higher in Yusho patients than in healthy subjects, while the proportion of regulatory T cells did not differ between groups. Serum concentrations of IL-36 and IFN-γ were significantly lower in Yusho patients than in healthy subjects. Conversely, serum cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), which is a cytokine related to activated NK cells, was higher in Yusho patients than in healthy subjects and was positively correlated with PCDF blood levels.
Increased numbers of NK cells in Yusho patients suggests that the innate immune response has been activated in Yusho patients. The seemingly paradoxical results for CTLA-4 and IFN-γ may reflect counterbalancing mechanisms preventing excessive NK cell activation. This dysregulation of innate immunity might contribute to the inflammation observed in Yusho patients.
1968 年在日本西部，受多氯联苯污染的“加美米油”被用于烹饪，导致许多人食物中毒。尤肖事件已经过去了 50 多年，虽然在尤肖患者中观察到了化脓等炎症性疾病，但这种炎症易感性的病因仍不清楚。
为了研究尤肖患者易发生炎症的机制，我们评估了来自长崎接受体检的尤肖患者和年龄匹配的健康对照者的血液样本中的外周免疫细胞亚群和炎症细胞因子浓度。
为了排除诊断的不确定性，我们测量了血清中多氯联苯（PCB）、多氯联苯四苯（PCQ）和多氯联苯二苯并呋喃（PCDF）的水平。通过流式细胞术分析免疫细胞（如自然杀伤细胞和调节性 T 细胞）群体。通过 ELISA 测量参与免疫细胞激活的血清细胞因子。
与健康对照组相比，尤肖患者的自然杀伤细胞比例较高，而调节性 T 细胞比例无差异。尤肖患者的血清白细胞介素 36（IL-36）和干扰素 γ（IFN-γ）浓度明显低于健康对照组。相反，细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）在尤肖患者中的血清浓度高于健康对照组，并且与 PCDF 血药浓度呈正相关。
尤肖患者中 NK 细胞数量的增加表明，尤肖患者的固有免疫反应已被激活。CTLA-4 和 IFN-γ 的看似矛盾的结果可能反映了防止 NK 细胞过度激活的平衡机制。这种固有免疫失调可能导致尤肖患者的炎症。
