Huaux F, Louahed J, Hudspith B, Meredith C, Delos M, Renauld J C, Lison D
Industrial Toxicology and Occupational Medicine Unit, International Institute of Cellular and Molecular Pathology, Faculty of Medicine, Catholic University of Louvain, Belgium.
Am J Respir Cell Mol Biol. 1998 Jan;18(1):51-9. doi: 10.1165/ajrcmb.18.1.2911.
There is evidence that, following exposure to crystalline silica, the release of several proinflammatory cytokines contributes to the induction of unbalanced inflammatory reaction leading to lung fibrosis. We have examined the potential contribution of interleukin-10 (IL-10), an anti-inflammatory cytokine, in the development of silicosis. In a mouse model of inflammatory lung reaction induced by intratracheal instillation of silica (0.5 mg and 5 mg DQ12/mouse), the levels of IL-10 protein (determined by ELISA) both in cells obtained after bronchoalveolar lavage (BAL) and in lung tissue homogenates were significantly increased when compared with controls. After in vitro lipopolysaccharide (LPS) stimulation (1 microg/ml), BAL cells obtained from silica-treated animals produced significantly more IL-10 protein and mRNA than cells obtained from control animals. To examine the role of IL-10 in the lung reaction induced by silica, IL-10-deficient animals were instilled with 5 mg of silica. Twenty-four hours after treatment, the amplitude of the inflammatory response (lactate dehydrogenase [LDH], protein and number of inflammatory cells in BAL) was significantly greater in IL-10-deficient animals than in the wild type. In contrast, the fibrotic response, evaluated by measuring lung hydroxyproline content and by histopathologic analysis 30 days after silica, was significantly less important in IL-10-deficient than in wild-type mice. Together, these data suggest that increased IL-10 synthesis induced by silica can limit the amplitude of the inflammatory reaction, but also contributes to amplify the lung fibrotic response.
有证据表明，接触结晶二氧化硅后，几种促炎细胞因子的释放会导致炎症反应失衡，进而引发肺纤维化。我们研究了抗炎细胞因子白细胞介素-10（IL-10）在矽肺发展中的潜在作用。在通过气管内注入二氧化硅（0.5毫克和5毫克DQ12/只小鼠）诱导的炎症性肺反应小鼠模型中，与对照组相比，支气管肺泡灌洗（BAL）后获得的细胞以及肺组织匀浆中的IL-10蛋白水平（通过ELISA测定）均显著升高。在体外脂多糖（LPS）刺激（1微克/毫升）后，来自二氧化硅处理动物的BAL细胞产生的IL-10蛋白和mRNA明显多于来自对照动物的细胞。为了研究IL-10在二氧化硅诱导的肺反应中的作用，向IL-10缺陷动物注入5毫克二氧化硅。处理24小时后，IL-10缺陷动物的炎症反应幅度（BAL中的乳酸脱氢酶[LDH]、蛋白和炎症细胞数量）明显大于野生型动物。相反，在二氧化硅处理30天后，通过测量肺羟脯氨酸含量和组织病理学分析评估的纤维化反应，在IL-10缺陷小鼠中比在野生型小鼠中明显不那么重要。总之，这些数据表明，二氧化硅诱导的IL-10合成增加可以限制炎症反应的幅度，但也有助于放大肺纤维化反应。
