L-cysteine Supplementation Attenuates Local Inflammation and Restores Gut Homeostasis in a Porcine Model of Colitis

Biochim Biophys Acta. 2009 Oct;1790(10):1161-9. doi: 10.1016/j.bbagen.2009.05.018. Epub 2009 Jun 9.

Abstract

Background: Inflammatory bowel disease (IBD), a chronic inflammation of the gastrointestinal tract, is characterized by a deregulation of the mucosal immune system and resistance of activated T cells to apoptosis. Current therapeutics show limited efficacy and potential toxicity; therefore there is a need for novel approaches for the treatment of IBD. L-cysteine was examined for its ability to reduce colitis symptoms and modulate local gene expression in a DSS-induced porcine model of colitis.

Methods: Colitis was induced via intra-gastric infusion of dextran sodium sulfate (DSS), followed by the administration of L-cysteine or saline. Clinical signs, morphological measurements, histology and gut permeability were assessed for the prognosis of colitis. Local tissue production of cytokines and gene expression in the colon were analyzed by ELISA and real-time RT-PCR.

Results: L-cysteine supplementation attenuated DSS-induced weight loss and intestinal permeability, reduced local chemokine expression and neutrophil influx, and markedly improved colon histology. Furthermore, cysteine significantly reduced the expression of pro-inflammatory cytokines, including TNF-alpha, IL-6, IL-12p40, IL-1beta, and resulted in increased expression of the apoptosis initiator caspase-8 and decreased expression of the pro-survival genes cFLIP and Bcl-xL.

Conclusions and general significance: These results suggest that L-cysteine administration aids in restoring gut immune homeostasis by attenuating inflammatory responses and restoring susceptibility of activated immune cells to apoptosis, and that cysteine supplementation may be a novel therapeutic strategy for the treatment of IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Caspase 8 / genetics
  • Colitis / chemically induced
  • Colitis / prevention & control*
  • Colon / drug effects
  • Colon / metabolism
  • Colon / pathology
  • Cysteine / administration & dosage*
  • Dextran Sulfate
  • Dietary Supplements
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Gastrointestinal Tract / drug effects*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / pathology
  • Gene Expression / drug effects
  • Homeostasis / drug effects*
  • Inflammation / prevention & control*
  • Interleukin-12 Subunit p40 / genetics
  • Interleukin-12 Subunit p40 / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism
  • Intestinal Absorption / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Swine
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-X Protein / genetics

Substances

  • Interleukin-12 Subunit p40
  • Interleukin-1beta
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • bcl-X Protein
  • Dextran Sulfate
  • Caspase 8
  • Cysteine