Nitazoxanide Suppresses IL-6 Production in LPS-stimulated Mouse Macrophages and TG-injected Mice

Int Immunopharmacol. 2012 May;13(1):23-7. doi: 10.1016/j.intimp.2012.03.002. Epub 2012 Mar 17.

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.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Culture Techniques
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Injections, Intraperitoneal
  • Interleukin-6 / antagonists & inhibitors*
  • Interleukin-6 / blood
  • Interleukin-6 / genetics
  • Lipopolysaccharides / pharmacology*
  • Macrophages, Peritoneal / drug effects*
  • Macrophages, Peritoneal / immunology
  • Male
  • Mice
  • Mice, Inbred Strains
  • Molecular Structure
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thiazoles / pharmacology*
  • Thioglycolates / pharmacology*
  • Transcription, Genetic / drug effects

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-6
  • Lipopolysaccharides
  • Thiazoles
  • Thioglycolates
  • lipopolysaccharide, E coli O55-B5
  • nitazoxanide