Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis

Arthritis Rheum. 2003 Jun;48(6):1701-7. doi: 10.1002/art.11035.


Objective: To examine whether systemic administration of immunostimulatory and immunosuppressive oligodeoxynucleotides (ODNs) alter host susceptibility to inflammatory arthritis.

Methods: Normal BALB/c mice were treated systemically with CpG ODNs or suppressive ODNs, and then challenged intraarticularly with CpG DNA. The onset and magnitude of the resulting inflammatory response was monitored.

Results: Systemic delivery of CpG ODNs significantly increased susceptibility to local inflammation, whereas systemic treatment with suppressive ODNs reduced this susceptibility. CD11c+ cells played a key role in mediating host sensitivity to arthritis. These cells were the dominant source of tumor necrosis factor alpha production in CpG-stimulated animals and transferred resistance to arthritis from mice treated with suppressive ODNs.

Conclusion: Systemic exposure to immunostimulatory and immunosuppressive DNA influences host susceptibility to local inflammatory challenge. Current findings raise the possibility that suppressive ODNs may be useful in the prevention/treatment of proinflammatory diseases.

MeSH terms

  • Adjuvants, Immunologic*
  • Adoptive Transfer
  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / pathology
  • Arthritis, Reactive / immunology*
  • Arthritis, Reactive / pathology
  • Cell Transplantation
  • CpG Islands / immunology*
  • Disease Models, Animal
  • Disease Susceptibility / immunology*
  • Dose-Response Relationship, Drug
  • Hindlimb
  • Injections, Intra-Articular
  • Joints / pathology
  • Mice
  • Mice, Inbred BALB C
  • Oligonucleotides / administration & dosage
  • Oligonucleotides / immunology*
  • Spleen / cytology
  • Spleen / immunology
  • Spleen / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Adjuvants, Immunologic
  • Oligonucleotides
  • Tumor Necrosis Factor-alpha