title: Inhibitory action of telithromycin against Shiga toxin and endotoxin.
abstract: Shiga toxin (Stx)-producing Escherichia coli (STEC) is associated with hemolytic uremic syndrome (HUS). High inflammatory cytokine [interleukin (IL)-6 and IL-8] levels and low anti-inflammatory cytokine (IL-10) levels are indicators of a high risk for developing HUS in STEC-infected children. In this study, we investigated inhibitory action of telithromycin, a ketolide, against STEC and against Stx and lipopolysaccharide (LPS). Telithromycin inhibited in vitro STEC growth without inducing Stx phage, in marked contrast to norfloxacin. Stx markedly induced inflammatory (but not anti-inflammatory) cytokine production in human peripheral blood monocytes, while LPS induced both inflammatory and anti-inflammatory cytokine production. Telithromycin selectively inhibited the IL-6 and IL-8 production from Stx-stimulated (but not LPS-stimulated) monocytes. The drug did not significantly inhibit IL-10 production. Our data suggest that Stx plays a crucial role in the stimulation of inflammatory cytokines and such inflammatory response is inhibited by telithromycin, an anti-bacterial agent.
authors.affiliation: Division of Bacteriology, Department of Infectious Disease Control and International Medicine, Niigata University Graduate School of Medical and Dental Sciences, 757 Ichibanchou, Asahimachidori, Niigata, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Nakagawa
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kojio
authors.forename: Ikue
authors.initials: I
authors.lastname: Taneike
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Iwakura
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tamura
authors.forename: Koji
authors.initials: K
authors.lastname: Kushiya
authors.forename: Fumio
authors.initials: F
authors.lastname: Gondaira
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D016207:Cytokines / Q000096:biosynthesis; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D006801:Humans; D066298:In Vitro Techniques; D048628:Ketolides; D008070:Lipopolysaccharides / Q000494:pharmacology; D018942:Macrolides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D022621:Shiga Toxin / Q000037:antagonists & inhibitors*
chemical_list: D016207:Cytokines; D004731:Endotoxins; D048628:Ketolides; D008070:Lipopolysaccharides; D018942:Macrolides; D022621:Shiga Toxin; C106791:telithromycin