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


CONCLUSIONS
Suppressive ODN may be of benefit in the treatment of chronic systemic autoimmune diseases such as systemic lupus erythematosus.
Dong
Li
L
Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892, USA.
Ito
Shuichi
S
Ishii
Ken J
KJ
Klinman
Dennis M
DM
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D001327:Autoimmune Diseases / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000276:immunology; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005921:Glomerulonephritis / Q000276:immunology / Q000517:prevention & control*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D051379:Mice; D008814:Mice, Inbred NZB; D009841:Oligonucleotides / Q000494:pharmacology* / Q000627:therapeutic use; D011507:Proteinuria / Q000517:prevention & control
D000974:Antibodies, Antinuclear; D016207:Cytokines; D009841:Oligonucleotides; D018664:Interleukin-12; D007371:Interferon-gamma; D004247:DNA