Protection from arthritis and myositis in a mouse model of acute chikungunya virus disease by bindarit, an inhibitor of monocyte chemotactic protein-1 synthesis

J Infect Dis. 2011 Oct 1;204(7):1026-30. doi: 10.1093/infdis/jir470.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphavirus Infections / blood
  • Alphavirus Infections / drug therapy*
  • Animals
  • Arthritis, Infectious / pathology
  • Arthritis, Infectious / prevention & control*
  • Arthritis, Infectious / virology
  • Chemokine CCL2 / antagonists & inhibitors*
  • Chemokine CCL2 / drug effects
  • Chemokine CCL2 / metabolism
  • Chikungunya Fever
  • Chikungunya virus*
  • Humans
  • Indazoles / pharmacology
  • Indazoles / therapeutic use*
  • Interferon-gamma / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Myositis / pathology
  • Myositis / prevention & control*
  • Myositis / virology
  • Propionates / pharmacology
  • Propionates / therapeutic use*
  • Tumor Necrosis Factor-alpha / metabolism
  • Viral Load / drug effects

Substances

  • Chemokine CCL2
  • Indazoles
  • Propionates
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • bindarit