title: Low-dose inorganic mercury increases severity and frequency of chronic coxsackievirus-induced autoimmune myocarditis in mice.
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 (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.
authors: Department of Pathology, Microbiology & Immunology, University of South Carolina School of Medicine, Columbia, South Carolina 29209, USA. jnyland@uscmed.sc.edu
authors: Jennifer F
authors: JF
authors: Nyland
authors: DeLisa
authors: D
authors: Fairweather
authors: Devon L
authors: DL
authors: Shirley
authors: Sarah E
authors: SE
authors: Davis
authors: Noel R
authors: NR
authors: Rose
authors: Ellen K
authors: EK
authors: Silbergeld
mesh_terms: D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000821:virology; D002311:Cardiomyopathy, Dilated / Q000139:chemically induced / Q000276:immunology / Q000473:pathology / Q000821:virology; D002908:Chronic Disease; D003384:Coxsackievirus Infections / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000821:virology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D029822:Enterovirus B, Human / Q000254:growth & development*; D004785:Environmental Pollutants / Q000633:toxicity*; D006321:Heart / Q000187:drug effects / Q000821:virology; D008297:Male; D017669:Mercury Compounds / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000139:chemically induced* / Q000276:immunology / Q000473:pathology / Q000821:virology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D012720:Severity of Illness Index; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D016207:Cytokines; D004785:Environmental Pollutants; D017669:Mercury Compounds