Celastrol inhibits pro-inflammatory cytokine secretion in Crohn's disease biopsies

Biochem Biophys Res Commun. 2004 Sep 24;322(3):778-86. doi: 10.1016/j.bbrc.2004.07.186.


Crohn's disease is a chronic intestinal inflammatory process. In modern therapy, TNF-alpha inhibition is the main goal. The aim here is to characterize the effects of Celastrol, a pentacyclic-triterpene, on the secretion of inflammatory cytokines by LPS-activated human cells. Celastrol dose-dependently inhibited the secretion of all tested pro-inflammatory cytokines with IC(50) in the nanomolar range. Effect not related to glucocorticoid receptor activity is shown by competition experiments with the steroid antagonist RU486. Celastrol inhibited the pro-inflammatory cytokine secretion from mucosal inflammatory biopsies from Crohn's disease patients. Cytometry emphasized that for all tested pro-inflammatory cytokines, CD33(+) cells are the most sensitive. Quantitative-PCR and confocal analysis on a human monocytic cell line indicated that Celastrol acts at the transcriptional level by inhibiting LPS-induced NF-kappaB translocation. Celastrol might be a putative anti-inflammatory drug in the treatment of inflammatory diseases, given its inhibition of cytokine production by intestinal biopsies from Crohn's disease patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cell Survival / drug effects
  • Cells, Cultured
  • Colon / drug effects
  • Colon / pathology*
  • Crohn Disease / pathology*
  • Cytokines / antagonists & inhibitors
  • Cytokines / biosynthesis*
  • Humans
  • Inflammation / physiopathology*
  • Lipopolysaccharides / toxicity
  • Monocytes
  • Receptors, Glucocorticoid / drug effects
  • Receptors, Glucocorticoid / physiology
  • Triterpenes / pharmacology*


  • Cytokines
  • Lipopolysaccharides
  • Receptors, Glucocorticoid
  • Triterpenes
  • tripterine