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Low Dose Inorganic Mercury Increases Severity and Frequency of Chronic Coxsackievirus induced Autoimmune Myocarditis in Mice, myocarditis

Low Dose Inorganic Mercury Increases Severity and Frequency of Chronic Coxsackievirus-induced Autoimmune Myocarditis in Mice


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JF Nyland, DL Fairweather, DL Shirley... - Toxicological ..., 2011 - Soc Toxicology Abstract 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 (i Hg) and organic mercury (including methyl mercury) have a range ...

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 (i Hg) 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 i Hg on a model of autoimmune heart disease in mice induced by infection with coxsackievirus B3. We examined the role of timing of i Hg exposure on disease; in some experiments mice were pretreated with i Hg (200μg/kg, every other day for 15 days) before disease induction with virus inoculation and in others they were treated with i Hg after the acute (viral) phase of disease, but before the development of dilated cardiomyopathy (DCM). i Hg alone had no effect on heart pathology. Pretreatment with i Hg before CVB3 infection significantly increased the severity of chronic myocarditis and DCM compared to control animals receiving vehicle alone. In contrast, treatment with i Hg after acute myocarditis did not affect the severity of chronic disease. The increased chronic myocarditis, fibrosis, and DCM induced by i Hg pretreatment were not due to increased viral replication in the heart, which was unaltered by i Hg treatment. i Hg pretreatment induced a macrophage infiltrate and mixed cytokine response in the heart during acute myocarditis, including significantly increased interleukin-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.

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Low Dose Inorganic Mercury Increases Severity and Frequency of Chronic Coxsackievirus-induced Autoimmune Myocarditis in Mice
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