| Title | Statins fail to improve outcome in experimental cerebral malaria and potentiate Toll-like receptor-mediated cytokine production by murine macrophages. | | Author(s) | Helmers AJ, Gowda DC, Kain KC, Liles WC | | Institution | Institute of Medical Science, and Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. | | Source | Am J Trop Med Hyg 2009 Oct; 81(4):631-7. | | MeSH | Animals
Antimalarials
Cells, Cultured
Gene Expression Regulation
Humans
Interleukin-6
Macrophages, Peritoneal
Malaria, Cerebral
Mice
Mice, Inbred C57BL
Parasitemia
Plasmodium berghei
Simvastatin
Toll-Like Receptor 2
Toll-Like Receptor 4
| | 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 pro-inflammatory cytokine production by primary murine macrophages. | | Language | eng | | Pub Type(s) | Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19815878 |
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