You are here
Statins fail to improve outcome in experimental cerebral malaria and potentiate Toll-like receptor-mediated cytokine production by murine macrophages.
Title | Statins fail to improve outcome in experimental cerebral malaria and potentiate Toll-like receptor-mediated cytokine production by murine macrophages. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Helmers, AJ, D Gowda, C, Kain, KC, W Liles, C |
Journal | Am J Trop Med Hyg |
Volume | 81 |
Issue | 4 |
Pagination | 631-7 |
Date Published | 2009 Oct |
ISSN | 1476-1645 |
Keywords | 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. |
DOI | 10.4269/ajtmh.2009.09-0204 |
Alternate Journal | Am. J. Trop. Med. Hyg. |
PubMed ID | 19815878 |