title: Modulation of tumor necrosis factor production by macrophages in Entamoeba histolytica infection.
abstract: The macrophage-derived mediator tumor necrosis factor alpha (TNF) is a cytokine with pleiotropic effects. TNF exhibits potent immunologic and inflammatory properties in parasitic diseases. The present study examined the production of TNF by macrophages isolated from gerbils infected with Entamoeba histolytica and by naive macrophages in response to amoebae in vitro. Amoebic liver abscess-derived macrophages produced low constitutive basal levels of TNF; in response to lipopolysaccharide (LPS) stimulation, TNF production was enhanced by 14-, 11-, and 6-fold at 10, 20, and 30 days postinfection, respectively. Amoebic liver abscess-derived macrophages pretreated with either recombinant gamma interferon (IFN-gamma) or the cyclooxygenase inhibitor indomethacin augmented TNF production in response to soluble amoebic proteins and LPS. Kupffer cells and peritoneal and spleen macrophages from infected animals did not release TNF constitutively in vitro. However, TNF production in response to LPS stimulation was significantly higher at 10 and 20 days postinfection. Macrophages from infected and naive animals pretreated with recombinant IFN-gamma or indomethacin produced increased amounts of TNF in response to LPS but not in response to soluble amoebic protein stimulation. Pretreatment of naive macrophages with amoebic proteins inhibited LPS-induced TNF production by 69 to 79%; the effect of the amoebic proteins was partially reversed by indomethacin pretreatment. In contrast, IFN-gamma- and LPS-activated naive macrophages produced enhanced levels of TNF in response to live amoebae and soluble amoebic proteins. Our results demonstrate that TNF production by macrophages is altered during E. histolytica infection and in response to amoebae and suggest a role for IFN-gamma and prostaglandin E2 in regulating TNF production during the infection.
authors.affiliation: Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Québec, Canada.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Keller
authors.forename: K
authors.initials: K
authors.lastname: Chadee
mesh_terms: D000818:Animals; D004749:Entamoebiasis / Q000378:metabolism*; D005849:Gerbillinae; D007728:Kupffer Cells / Q000378:metabolism; D008070:Lipopolysaccharides; D008101:Liver Abscess, Amebic / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D015800:Protozoan Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D008070:Lipopolysaccharides; D015800:Protozoan Proteins; D014409:Tumor Necrosis Factor-alpha