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.