Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA.
Toxicol Sci. 2012 Jan;125(1):134-43. doi: 10.1093/toxsci/kfr264. Epub 2011 Oct 9.
Mercury is a widespread environmental contaminant with neurotoxic impacts that have been observed over a range of exposures. In addition, there is increasing evidence that inorganic mercury (iHg) and organic mercury (including methyl mercury) have a range of immunotoxic effects, including immune suppression and induction of autoimmunity. In this study, we investigated the effect of iHg on a model of autoimmune heart disease in mice induced by infection with coxsackievirus B3 (CVB3). We examined the role of timing of iHg exposure on disease; in some experiments, mice were pretreated with iHg (200 μg/kg, every other day for 15 days) before disease induction with virus inoculation, and in others, they were treated with iHg after the acute (viral) phase of disease but before the development of dilated cardiomyopathy (DCM). iHg alone had no effect on heart pathology. Pretreatment with iHg before CVB3 infection significantly increased the severity of chronic myocarditis and DCM compared with control animals receiving vehicle alone. In contrast, treatment with iHg after acute myocarditis did not affect the severity of chronic disease. The increased chronic myocarditis, fibrosis, and DCM induced by iHg pretreatment were not due to increased viral replication in the heart, which was unaltered by iHg treatment. iHg pretreatment induced a macrophage infiltrate and mixed cytokine response in the heart during acute myocarditis, including significantly increased interleukin (IL)-12, IL-17, interferon-γ, and tumor necrosis factor-α levels. IL-17 levels were also significantly increased in the spleen during chronic disease. Thus, we show for the first time that low-dose Hg exposure increases chronic myocarditis and DCM in a murine model.
汞是一种广泛存在的环境污染物，具有神经毒性影响，已在一系列暴露中观察到。此外，越来越多的证据表明无机汞（iHg）和有机汞（包括甲基汞）具有一系列免疫毒性作用，包括免疫抑制和自身免疫诱导。在这项研究中，我们研究了 iHg 对柯萨奇病毒 B3（CVB3）感染诱导的自身免疫性心脏病小鼠模型的影响。我们研究了 iHg 暴露时间对疾病的影响；在一些实验中，在病毒接种诱导疾病之前，用 iHg（200μg/kg，每隔一天，共 15 天）预处理小鼠，而在其他实验中，在急性（病毒）期后用 iHg 处理，但在扩张型心肌病（DCM）发展之前。iHg 本身对心脏病理学没有影响。在 CVB3 感染前用 iHg 预处理显著增加了慢性心肌炎和 DCM 的严重程度，与单独接受载体的对照动物相比。相比之下，在急性心肌炎后用 iHg 治疗并不影响慢性疾病的严重程度。与单独接受载体的对照动物相比，iHg 预处理在慢性疾病中诱导的慢性心肌炎、纤维化和 DCM 的增加不是由于心脏中的病毒复制增加，而 iHg 治疗并未改变病毒复制。iHg 预处理在急性心肌炎期间诱导心脏中巨噬细胞浸润和混合细胞因子反应，包括显著增加白细胞介素（IL）-12、IL-17、干扰素-γ 和肿瘤坏死因子-α水平。在慢性疾病期间，脾脏中的 IL-17 水平也显著增加。因此，我们首次表明，低剂量 Hg 暴露会增加小鼠模型中的慢性心肌炎和 DCM。
