title: Nitazoxanide suppresses IL-6 production in LPS-stimulated mouse macrophages and TG-injected mice.
abstract: Suppression of interleukin (IL)-6 production has beneficial effects against various inflammatory diseases. Through a rapid screening system, we found that nitazoxanide, or 2-acetyloxy-N-(5-nitro-2-thiazolyl) benzamide, which is a well-known antiparasitic agent, suppressed lipopolysaccharide (LPS)-induced production of IL-6 from RAW 264.7 cells and mouse peritoneal macrophages, with 50% inhibitory concentrations (IC(50)s) of 1.54 mM and 0.17 mM, respectively. Nitazoxanide also inhibited the LPS-induced expression of IL-6 mRNA in RAW 264.7 cells. To investigate the effects of nitazoxanide in vivo, we orally administered nitazoxanide at a dose of 100mg/kg to mice 2h before a 1-mL intraperitoneal injection of 4% thioglycollate (TG). Six hours after TG injection, plasma IL-6 levels were markedly lower (by 90%) than the levels in vehicle-treated mice. These data suggest that nitazoxanide could be a promising lead compound for agents against various diseases associated with overproduction of IL-6.
authors.affiliation: Department of Immunology, College of VeterinaryMedicine, Konkuk University, 1 Hwayang-Dong, Gwangjin-Gu, Seoul, Republic of Korea.
authors.forename: Seong Keun
authors.initials: SK
authors.lastname: Hong
authors.forename: Hee Joo
authors.initials: HJ
authors.lastname: Kim
authors.forename: Chang Seon
authors.initials: CS
authors.lastname: Song
authors.forename: In Soo
authors.initials: IS
authors.lastname: Choi
authors.forename: Joong Bok
authors.initials: JB
authors.lastname: Lee
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Park
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D009574:Nitro Compounds; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology*; D013864:Thioglycolates / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015850:Interleukin-6; D008070:Lipopolysaccharides; D009574:Nitro Compounds; D013844:Thiazoles; D013864:Thioglycolates; D000093242:Interleukin-6 Inhibitors; C482199:lipopolysaccharide, E coli O55-B5; C041747:nitazoxanide