1921
Volume 81, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Cerebral malaria is responsible for a large proportion of the estimated one million deaths caused by malaria annually. This disease is associated with excessive pro-inflammatory cytokine production resulting from dysregulated host responses to infection. On the basis of reports indicating potent activity against host-mediated inflammatory disorders such as sepsis, we examined the activity of statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) on malaria-associated inflammation and . Simvastatin failed to improve survival or alter parasitemia in C57BL/6 mice infected with ANKA, an experimental model of cerebral malaria. statin treatment potentiated production of tumor necrosis factor and interleukin-6 by murine peritoneal macrophages in response to glycosylphosphatidyl inositol, a Toll-like receptor 2 (TLR2) ligand. Statin treatment also potentiated pro-inflammatory cytokine production stimulated by a panel of TLR2 and TLR4 ligands. Our results indicate that statins fail to confer protection in experimental cerebral malaria and potentiate TLR-mediated pro-inflammatory cytokine production by primary murine macrophages.

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  • Received : 21 Apr 2009
  • Accepted : 16 Jun 2009

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