Abstract
Chikungunya virus (CHIKV) is associated with outbreaks of infectious rheumatic disease in humans. Using a mouse model of CHIKV arthritis and myositis, we show that tumor necrosis factor-α, interferon-γ, and monocyte chemotactic protein 1 (MCP-1) were dramatically induced in tissues from infected mice. The same factors were detected in the serum of patients with CHIKV-induced polyarthralgia and polyarthritis, with MCP-1 levels being particularly elevated. Bindarit (MCP inhibitor) treatment ameliorated CHIKV disease in mice. Histological analysis of muscle and joint tissues showed a reduction in inflammatory infiltrate in infected mice treated with bindarit. These results suggest that bindarit may be useful in treating CHIKV-induced arthritides in humans.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alphavirus Infections / blood
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Alphavirus Infections / drug therapy*
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Animals
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Arthritis, Infectious / pathology
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Arthritis, Infectious / prevention & control*
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Arthritis, Infectious / virology
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Chemokine CCL2 / antagonists & inhibitors*
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Chemokine CCL2 / drug effects
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Chemokine CCL2 / metabolism
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Chikungunya Fever
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Chikungunya virus*
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Humans
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Indazoles / pharmacology
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Indazoles / therapeutic use*
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Interferon-gamma / metabolism
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Mice
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Mice, Inbred C57BL
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Models, Animal
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Myositis / pathology
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Myositis / prevention & control*
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Myositis / virology
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Propionates / pharmacology
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Propionates / therapeutic use*
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Tumor Necrosis Factor-alpha / metabolism
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Viral Load / drug effects
Substances
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Chemokine CCL2
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Indazoles
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Propionates
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Tumor Necrosis Factor-alpha
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Interferon-gamma
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bindarit