Statins fail to improve outcome in experimental cerebral malaria and potentiate toll-like receptor-mediated cytokine production by murine macrophages

Andrew J. Helmers, D. Channe Gowda, Kevin C. Kain, W. Conrad Liles

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Cerebral malaria is responsible for a large proportion of the estimated one million deaths caused by Plasmodium falciparum 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 in vivo and in vitro. Simvastatin failed to improve survival or alter parasitemia in C57BL/6 mice infected with Plasmodium berghei ANKA, an experimental model of cerebral malaria. In vitro statin treatment potentiated production of tumor necrosis factor and interleukin-6 by murine peritoneal macrophages in response to P falciparum 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 proinflammatory cytokine production by primary murine macrophages.

Original languageEnglish (US)
Pages (from-to)631-637
Number of pages7
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume81
Issue number4
DOIs
StatePublished - Oct 2009

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Infectious Diseases
  • Virology

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