Beryllium exposure in susceptible individuals leads to the development of chronic beryllium disease, a lung disorder marked by release of inflammatory cytokine and granuloma formation. We have previously reported that beryllium induces an immune response even in blood mononuclear cells from healthy individuals. In this study, we investigate the effects of beryllium on lipopolysaccharide-mediated cytokine release in blood mononuclear and dendritic cells from healthy individuals. We found that in vitro treatment of beryllium sulfate inhibits the secretion of lipopolysaccharide-mediated interleukin 10, while the release of interleukin 1beta is enhanced. In addition, not all lipopolysaccharide-mediated responses are altered, as interleukin 6 release in unaffected upon beryllium treatment. Beryllium sulfate-treated cells show altered phosphotyrosine levels upon lipopolysaccharide stimulation. Significantly, beryllium inhibits the phosphorylation of signal transducer and activator of transducer 3, induced by lipopolysaccharide. Finally, inhibitors of phosphoinositide-3 kinase mimic the effects of beryllium in inhibition of interleukin 10 release, while they have no effect on interleukin 1beta secretion. This study strongly suggests that prior exposures to beryllium could alter host immune responses to bacterial infections in healthy individuals, by altering intracellular signaling.

中文翻译：

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铍改变人外周血单核细胞中脂多糖介导的细胞内磷酸化和细胞因子释放。

易感人群中的铍暴露会导致慢性铍病的发展，这是一种以释放炎性细胞因子和肉芽肿形成为特征的肺部疾病。我们之前曾报道，铍即使在健康个体的血液单核细胞中也能诱导免疫反应。在这项研究中，我们研究了铍对健康个体血液单核细胞和树突细胞中脂多糖介导的细胞因子释放的影响。我们发现硫酸铍的体外处理抑制了脂多糖介导的白介素 10 的分泌，而白介素 1β 的释放得到了增强。此外，并非所有脂多糖介导的反应都会改变，因为白介素 6 的释放不受铍处理的影响。硫酸铍处理的细胞在脂多糖刺激下显示改变的磷酸酪氨酸水平。重要的是，铍抑制由脂多糖诱导的信号转导和转导 3 激活剂的磷酸化。最后，磷酸肌醇 3 激酶抑制剂模拟铍在抑制白细胞介素 10 释放方面的作用，而它们对白细胞介素 1β 分泌没有影响。这项研究强烈表明，先前接触铍可以通过改变细胞内信号传导来改变健康个体对细菌感染的宿主免疫反应。磷酸肌醇 3 激酶抑制剂模拟铍在抑制白细胞介素 10 释放方面的作用，而它们对白细胞介素 1β 分泌没有影响。这项研究强烈表明，先前接触铍可以通过改变细胞内信号传导来改变健康个体对细菌感染的宿主免疫反应。磷酸肌醇 3 激酶抑制剂模拟铍在抑制白细胞介素 10 释放方面的作用，而它们对白细胞介素 1β 分泌没有影响。这项研究强烈表明，先前接触铍可以通过改变细胞内信号传导来改变健康个体对细菌感染的宿主免疫反应。