CpG motifs of bacterial DNA exacerbate colitis of dextran sulfate sodium-treated mice

Eur J Immunol. 2002 Jul;32(7):2084-92. doi: 10.1002/1521-4141(200207)32:7<2084::AID-IMMU2084>3.0.CO;2-Q.


Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal immune response with elevated levels of the Th1 cytokines TNF, IL-12 and IFN-gamma. The luminal flora has been implicated as a major factor contributing to the initiation and perpetuation of chronic intestinal inflammation by as yet unknown mechanisms. Bacterial DNA contains unmethylated cytosine-guanosine dinucleotides (CpG) which strongly activate Th1-mediated immune responses. To test whether these CpG-motifs contribute to intestinal inflammation we treated mice with dextran-sulfate-sodium (DSS)-induced acute or chronic colitis for 5 days with CpG-containing oligodeoxynucleotides (CpG-ODN). Colonic inflammation was assessed by histological scoring. Colonic cytokine RNA was quantified by reverse transcription-PCR and cytokine secretion from mesenterial lymph node cells by ELISA. In chronic colitis, CpG-ODN treatment severely aggravated inflammation by 50%. Colonic expression of IFN-gamma and TNF was elevated (200- and 150-fold, respectively) and IFN-gamma and IL-12 secretion from lymph node cells was increased 5,000- and 8-fold, respectively, compared to GpG-ODN-treated controls. Similar effects were obtained in acute colitis. In conclusion, CpG-motifs of bacterial DNA have proinflammatory activity by strengthening the Th1 arm of immunity in DSS-induced colitis, and might therefore play a significant role in the initiation and perpetuation of inflammation in IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adjuvants, Immunologic* / pharmacology
  • Animals
  • Chronic Disease
  • Colitis / chemically induced
  • Colitis / drug therapy
  • Colitis / immunology*
  • CpG Islands / immunology*
  • Cytokines / metabolism
  • DNA, Bacterial / immunology*
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Female
  • Interferon-gamma / immunology
  • Lipopolysaccharides / immunology
  • Lipopolysaccharides / pharmacology
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Mesentery
  • Mice
  • Mice, Inbred BALB C
  • Neutralization Tests
  • Oligodeoxyribonucleotides / immunology*
  • Oligodeoxyribonucleotides / pharmacology
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*
  • Tumor Cells, Cultured


  • Adjuvants, Immunologic
  • CPG-oligonucleotide
  • Cytokines
  • DNA, Bacterial
  • Lipopolysaccharides
  • Oligodeoxyribonucleotides
  • Interferon-gamma
  • Dextran Sulfate