Anisodamine inhibits shiga toxin type 2-mediated tumor necrosis factor-alpha production in vitro and in vivo

Exp Biol Med (Maywood). 2001 Jun;226(6):597-604. doi: 10.1177/153537020122600614.


Cytokines, in particular tumor necrosis factor (TNF), appear to be necessary to develop the pathological process of Shiga toxin-producing Escherichia coli (STEC) infection. In this study we examined the effect of anisodamine, a vasoactive drug, on TNF-alpha production in Shiga toxin type 2 (Stx2)-stimulated human monocytic cells in vitro and in Stx2-injected mice sera in vivo. Human monocytes and THP-1 cells were stimulated by Stx2 (1-100 ng/ml) with or without anisodamine addition (1-400 micrograms/ml). For in vivo evaluations, C57BL/6 mice were given a single intraperitoneal injection of anisodamine (6-50 mg/kg) or saline after intraperitoneal injection of Stx2 (50 ng/kg). The results showed that anisodamine suppressed Stx2-induced TNF-alpha production in a dose- and time-dependent manner. Anisodamine also suppressed Stx2-induced TNF-alpha mRNA expression. Further study showed that endogenous prostaglandin E2 may be involved in this inhibitory effect. In contrast to TNF-alpha mRNA, anisodamine at concentrations as high as 400 micrograms/ml did not decrease Stx2-induced IL-1 beta and IL-8 mRNA levels. In addition, anisodamine (> 50 micrograms/ml) increased Stx2-stimulated THP-1 cell viability. Levels of TNF-alpha in anisodamine-treated mice sera were significantly lower than those in the saline-treated group 1.5 and 24 hr after Stx2 injection. Anisodamine induced a lower percentage of death in Stx2-injected mice. Taken together, our results indicate that anisodamine has an important regulatory effect on Stx2-induced TNF-alpha production in vitro and in vivo. The present study suggested that this drug should be further investigated for its effects on Stx2-mediated diseases in humans.

MeSH terms

  • Animals
  • Cell Line
  • Cell Survival
  • Cells, Cultured
  • Dinoprostone / metabolism
  • Drugs, Chinese Herbal / pharmacology
  • Gene Expression
  • Humans
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / genetics
  • Interleukin-10 / biosynthesis
  • Interleukin-10 / genetics
  • Interleukin-8 / biosynthesis
  • Interleukin-8 / genetics
  • Mice
  • Mice, Inbred C57BL
  • Monocytes / immunology
  • Shiga Toxin 2 / antagonists & inhibitors*
  • Shiga Toxin 2 / immunology
  • Shiga Toxin 2 / pharmacology
  • Solanaceous Alkaloids / metabolism
  • Solanaceous Alkaloids / pharmacology*
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics


  • Drugs, Chinese Herbal
  • Interleukin-1
  • Interleukin-8
  • Shiga Toxin 2
  • Solanaceous Alkaloids
  • Tumor Necrosis Factor-alpha
  • anisodamine
  • Interleukin-10
  • Dinoprostone