| Sustained high levels of interleukin-6 contribute to the pathogenesis of enterovirus 71 in a neonate mouse model. | |
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MedLine Citation:
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PMID: 21228224 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Enterovirus 71 (EV71) is the major causative agent of hand, foot, and mouth disease (HFMD) in young children and has been consistently associated with the most severe complications of the disease, including central nervous system inflammation and pulmonary edema. Increasing frequency and amplitude of EV71 outbreaks have raised awareness and concerns worldwide. Previous reports proposed that overwhelming virus replication combined with the induction of massive proinflammatory cytokines is responsible for the pathogenicity of EV71. Specifically, elevated interleukin-6 (IL-6) levels were observed consistently in patients and strongly correlated with disease severity. In this study, we show in the neonate mouse model that sustained high levels of IL-6 produced upon EV71 infection lead to severe tissue damage and eventually death of the animals. Administration of anti-IL-6 neutralizing antibodies after the onset of the clinical symptoms successfully improved the survival rates and clinical scores of the infected hosts. Compared to untreated infected controls, anti-IL-6-treated mice displayed reduced tissue damage, absence of splenic atrophy, and increased immune cell activation. In addition, markedly elevated systemic levels of IL-10 were measured in the protected animals. Furthermore, there was no significant difference in virus titers between anti-IL-6-treated mice and untreated mice, indicating that the anti-IL-6 antibody-mediated protection is independent of the virus load. Our findings thus demonstrate that IL-6 plays a major role in EV71-induced immunopathogenesis. As there is still neither vaccine nor treatment available against EV71, anti-IL-6 antibody treatment represents a potential therapeutic approach to providing protection from the most severe complications of the disease. |
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Authors:
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Wei Xin Khong; Damian G W Foo; Scott L Trasti; Eng Lee Tan; Sylvie Alonso |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-01-12 |
Journal Detail:
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Title: Journal of virology Volume: 85 ISSN: 1098-5514 ISO Abbreviation: J. Virol. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-03-16 Completed Date: 2011-05-13 Revised Date: 2012-04-27 |
Medline Journal Info:
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Nlm Unique ID: 0113724 Medline TA: J Virol Country: United States |
Other Details:
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Languages: eng Pagination: 3067-76 Citation Subset: IM |
Affiliation:
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Department of Microbiology, Immunology Programme, Yong Loo Lin School of Medicine, National University of Singapore, CeLS Building 03-05, 28 Medical Drive, Singapore 117597, Republic of Singapore. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Animals, Newborn Disease Models, Animal Enterovirus A, Human / pathogenicity* Enterovirus Infections / immunology*, pathology*, virology Histocytochemistry Interleukin-6 / biosynthesis*, immunology, toxicity* Intestines / pathology Mice Mice, Inbred BALB C Muscles / pathology Severity of Illness Index Spleen / pathology Survival Analysis Viral Load |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-6 |
| Comments/Corrections | |
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