Effect of endocrine disrupting chemicals on lipopolysaccharide-induced tumor necrosis factor-alpha and nitric oxide production by mouse macrophages.
Little is known about the development of infectious diseases during exposure to endocrine disrupting chemicals (EDCs), although several studies have reported on the effect of EDCs on the immune function of the human body. To assess the effect of EDCs on the development of infectious disease, we investigated the effect of eighteen possible EDCs on mouse macrophage production of tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) in response to bacterial endotoxin in vitro and ex vivo. Of chemicals we examined, simazine, nitrofen, and benzyl butyl phthalate inhibited lipopolysaccharide (LPS)-induced TNF-alpha production by mouse macrophage cell line RAW 264 in vitro. Carbaryl, alachlor, nonylphenol, octylphenol, tributyltin, and triphenyltin inhibited LPS-induced NO production in vitro, whereas 2,4-dichlorophenoxy acetic acid and bisphenol A enhanced its production. Zineb and alachlor, on the other hand, enhanced LPS-induced TNF-alpha production by mouse peritoneal macrophages ex vivo, while alachlor inhibited LPS/interferon-gamma-induced NO production ex vivo. These results indicate that some EDCs exert modulatory activity on endotoxin-induced macrophage activation either positively or negatively, suggesting that these compounds may affect the development of infectious diseases. This is the first report that systematically compared the effect of EDCs on LPS action.
Hong
Chih-Chun
CC
Division of Microbiology, National Institute of Health Sciences, Tokyo, Japan.
Shimomura-Shimizu
Mifumi
M
Muroi
Masashi
M
Tanamoto
Ken-ichi
K
D000818:Animals; D002460:Cell Line; D004147:Dioxins / Q000494:pharmacology; D004347:Drug Interactions; D004703:Endocrine System / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000494:pharmacology*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis*; D010575:Pesticides / Q000494:pharmacology; D010968:Plasticizers / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004147:Dioxins; D004785:Environmental Pollutants; D008070:Lipopolysaccharides; D010575:Pesticides; D010968:Plasticizers; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide