BACKGROUND 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. OBJECTIVES 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. METHODS 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. RESULTS 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. CONCLUSION 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.

中文翻译：

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深入了解“ Yusho”的先天免疫反应：天然杀伤细胞和调节性T细胞对Yusho患者易发炎性素质的影响。

背景技术1968年，在日本西部，烹饪中使用了多氯联苯污染的“ Kanimi米油”，导致许多人食物中毒。自Yusho事件以来已经过去了50多年，尽管在Yusho患者中发现了化脓等炎症性疾病，但这种炎症易感性的病因仍不清楚。目的为了研究Yusho患者的炎症易感性机制，评估了从Yusho患者和在长崎进行医学检查的年龄匹配的健康受试者收集的血液样本中的外周免疫细胞分数和炎症细胞因子的浓度。方法为了排除诊断不确定性，血清多氯联苯（PCB），多氯联苯（PCQ），测定了多氯二苯并呋喃（PCDF）。通过流式细胞术分析了免疫细胞（例如自然杀伤和调节性T细胞）种群。通过ELISA测量参与免疫细胞活化的血清细胞因子。结果Yusho患者中自然杀伤细胞的相对比例高于健康受试者，而两组间调节性T细胞的比例无差异。Yusho患者的血清IL-36和IFN-γ浓度显着低于健康受试者。相反，Yusho患者的血清细胞毒性T淋巴细胞相关抗原4（CTLA-4）是与活化的NK细胞相关的细胞因子，高于健康受试者，并且与PCDF血液水平呈正相关。结论Yusho患者的NK细胞数量增加表明Yusho患者的先天免疫反应已被激活。CTLA-4和IFN-γ的看似矛盾的结果可能反映了防止过度NK细胞活化的平衡机制。先天免疫力的这种失调可能导致在Yusho患者中观察到的炎症。