Inhibitory action of telithromycin against Shiga toxin and endotoxin

• Published in: Biochemical and biophysical research communications Vol. 310; no. 4; pp. 1194 - 1199
• Main Authors: Nakagawa, Saori, Kojio, Seiichi, Taneike, Ikue, Iwakura, Nobuhiro, Tamura, Yukiko, Kushiya, Koji, Gondaira, Fumio, Yamamoto, Tatsuo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 31.10.2003
• Subjects: Adult; Cytokine; Cytokines - biosynthesis; Endotoxin; Endotoxins - antagonists & inhibitors; Escherichia coli; Humans; In Vitro Techniques; Ketolides; Lipopolysaccharides - pharmacology; Macrolides - pharmacology; Monocytes - drug effects; Monocytes - metabolism; Phage; Shiga toxin; Shiga Toxin - antagonists & inhibitors; Telithromycin; Telithromycin; Shiga toxin; Endotoxin; Escherichia coli; Cytokine; Phage
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2003.09.145

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.