title: Imidocarb, a potent anti-protozoan drug, up-regulates interleukin-10 production by murine macrophages.
abstract: Interleukin-10 (IL-10), a potent antiinflammatory and immunosuppressive cytokine, plays an important role in the regulation of immune responses. To discover small molecules that stimulate IL-10 production, a cell-based screening assay was performed using a murine macrophage cell line, RAW264.7. Imidocarb, (3,3'-bis-2-imidazolin-2-yl)-carbanilide, which has been used as an anti-protozoan drug for the prevention and treatment of babesiosis in cattle, was thus identified. Imidocarb markedly enhanced LPS-induced IL-10 production not only by RAW264.7 cells but also by murine peritoneal macrophages in a concentration-dependent manner. It also augmented IL-10 production in the presence of zymosan, a yeast cell wall component. In contrast, imidocarb inhibited LPS-induced tumor necrosis factor (TNF)-alpha production by peritoneal macrophages. In mice, intraperitoneal administration of imidocarb significantly increased serum IL-10 levels and lowered TNF-alpha levels. Our results suggest that a novel anti-inflammatory property of imidocarb could lead to new therapeutic approaches in inflammatory conditions.
authors.affiliation: Daiichi Suntory Biomedical Research Co., Ltd., 1-1-1 Wakayamadai, Shimamoto-cho, Mishima-gun, Osaka 618-8513, Japan.
authors.forename: Toyoko
authors.initials: T
authors.lastname: Katayama
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nagahira
authors.forename: Kyoko
authors.initials: K
authors.lastname: Konishi
authors.forename: Kozo
authors.initials: K
authors.lastname: Yamaichi
authors.forename: Shinzo
authors.initials: S
authors.lastname: Oikawa
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D007095:Imidocarb / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D015854:Up-Regulation / Q000187:drug effects; D015054:Zymosan / Q000494:pharmacology
chemical_list: D000981:Antiprotozoal Agents; D008070:Lipopolysaccharides; D016753:Interleukin-10; D007095:Imidocarb; D015054:Zymosan