Statins potentiate macrophage inflammation
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Statins fail to improve outcome in experimental cerebral malaria and
potentiate Toll-like receptor-mediated cytokine production by murine
macrophages.
Helmers AJ, Gowda DC, Kain KC, Liles WC.
Institute of Medical Science, and Division of Infectious Diseases,
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
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.
Publication Types:
* Research Support, Non-U.S. Gov't
PMID: 19815878