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. CONCLUSION: Suppressive ODNs may be of therapeutic value in the treatment of RA, and potentially other autoimmune diseases.