Suppression of prostaglandin E2 by malaria parasite products and antipyretics promotes overproduction of tumor necrosis factor-alpha: association with the pathogenesis of childhood malarial anemia.

The Journal of Infectious Diseases
Christopher C KellerDouglas J Perkins

Abstract

Cytokines and effector molecules are important immunoregulatory molecules in human malaria. Tumor necrosis factor (TNF)-alpha limits malaria parasitemia but also promotes pathogenesis at high concentrations, whereas prostaglandin E2 (PGE2) inhibits TNF-alpha production and is reduced in childhood malaria, at least in part, through suppression of cyclooxygenase (COX)-2 following the ingestion of Plasmodium falciparum hemozoin (pfHz; malarial pigment) by peripheral blood mononuclear cells (PBMCs). Although molecular interactions between TNF-alpha and PGE2 are largely unexplored in human malaria, results presented here show that pfHz-induced suppression of PBMC COX-2 gene products induces overproduction of TNF-alpha. Moreover, addition of exogenous PGE2 to pfHz-treated PBMCs dose-dependently decreased TNF-alpha production, whereas experimental COX inhibitors and antipyretics used during human malaria generated increased TNF-alpha production. Healthy, malaria-exposed children had elevated levels of circulating bicyclo-PGE2/TNF-alpha, compared with children with malarial anemia (P<.01), with systemic bicyclo-PGE2 and TNF-alpha significantly associated with hemoglobin concentrations (r=0.745; P<.01). The results of the present study ...Continue Reading

Citations

Jul 3, 2013·Microbes and Infection·Abdur RubYusuf Akhter
Dec 18, 2008·The Journal of Infectious Diseases·Peter Gottfried KremsnerTerrie Taylor
Jun 17, 2009·Infection and Immunity·Christopher C KellerDouglas J Perkins
Oct 13, 2006·Malaria Journal·Ian A ClarkWilliam B Cowden
Nov 24, 2011·International Journal of Biological Sciences·Douglas J PerkinsJohn Michael Ong'echa
Mar 29, 2014·Advances in Pharmacological Sciences·Chibueze Peter IhekweremeEdward Chieke Nwanegbo
Dec 15, 2015·FEMS Microbiology Reviews·Katrien DeroostPhilippe E Van den Steen
Feb 28, 2007·Cellular Microbiology·Daniel CarapauAna Rodriguez
Aug 21, 2014·Memórias do Instituto Oswaldo Cruz·Susana RamosHenrique Silveira
Sep 28, 2007·The Lancet Infectious Diseases·Thomas HänscheidMartin P Grobusch
Mar 5, 2010·American Journal of Hematology·Anuraj H Shankar, Wafaie W Fawzi
Jun 22, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Bruno B AndradeManoel Barral-Netto
Nov 24, 2020·Trends in Parasitology·Thao-Thy PhamPhilippe E Van den Steen

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