Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus-prone NZB x NZW mice

Arthritis Rheum. 2005 Feb;52(2):651-8. doi: 10.1002/art.20810.


Objective: Synthetic oligodeoxynucleotides (ODN) expressing TTAGGG motifs suppress the production of proinflammatory cytokines and have been proven effective at blocking the development of certain organ-specific autoimmune diseases. We undertook this study to determine whether suppressive ODN alter the development of systemic autoimmunity, by evaluating their effect on the progression of lupus-like disease in NZB x NZW (NZB/NZW) mice.

Methods: We repeatedly treated mice with suppressive ODN before or after the onset of proteinuria. We monitored the effect of treatment on the onset, severity, and immunologic correlates of disease.

Results: Treatment with suppressive ODN significantly prolonged lifespan while delaying the onset and progression of glomerulonephritis in NZB/NZW mice. Clinical improvement was accompanied by a significant reduction in anti-double-stranded DNA autoantibody production and by significantly reduced secretion of interferon-gamma and interleukin-12 in vivo.

Conclusion: Suppressive ODN may be of benefit in the treatment of chronic systemic autoimmune diseases such as systemic lupus erythematosus.

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Autoimmune Diseases / prevention & control
  • Cytokines / biosynthesis*
  • DNA / immunology
  • Disease Progression
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Glomerulonephritis / immunology
  • Glomerulonephritis / prevention & control*
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Kidney / pathology
  • Mice
  • Mice, Inbred NZB
  • Oligonucleotides / pharmacology*
  • Oligonucleotides / therapeutic use
  • Proteinuria / prevention & control


  • Antibodies, Antinuclear
  • Cytokines
  • Oligonucleotides
  • Interleukin-12
  • Interferon-gamma
  • DNA