Suppressive oligonucleotides protect against collagen-induced arthritis in mice.
OBJECTIVE
To examine whether systemic administration of oligonucleotides (ODNs), known to inhibit the production of proinflammatory cytokines, alters host susceptibility to collagen-induced arthritis (CIA), a murine model of rheumatoid arthritis (RA).


METHODS
CIA was induced by injecting DBA/1 mice with type II collagen (CII) in Freund's complete adjuvant, followed 3 weeks later by CII in Freund's incomplete adjuvant. The effect of suppressive ODNs on the incidence and severity of disease was monitored, as were immune correlates of CIA.


RESULTS
Suppressive ODNs administered during the inductive phase of CIA significantly reduced the incidence and severity of arthritis. Treatment with suppressive ODNs significantly decreased serum titers of pathogenic IgG anti-CII autoantibodies and interferon-gamma production by collagen-reactive T cells.


CONCLUSIONS
Suppressive ODNs may be of therapeutic value in the treatment of RA, and potentially other autoimmune diseases.
Dong
Li
L
CBER/FDA, US Food and Drug Administration, Building 29A, Room 3D10, Bethesda, MD 20892, USA.
Ito
Shu-ichi
S
Ishii
Ken J
KJ
Klinman
Dennis M
DM
D000818:Animals; D000906:Antibodies; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control*; D024043:Collagen Type II / Q000276:immunology* / Q000494:pharmacology; D000939:Epitopes; D005620:Freund's Adjuvant / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009841:Oligonucleotides / Q000494:pharmacology*; D018417:Th1 Cells / Q000378:metabolism
D000906:Antibodies; D024043:Collagen Type II; D000939:Epitopes; D009841:Oligonucleotides; D007371:Interferon-gamma; D005620:Freund's Adjuvant