Influence of stimulatory and suppressive DNA motifs on host susceptibility to inflammatory arthritis.
OBJECTIVE
To examine whether systemic administration of immunostimulatory and immunosuppressive oligodeoxynucleotides (ODNs) alter host susceptibility to inflammatory arthritis.


METHODS
Normal BALB/c mice were treated systemically with CpG ODNs or suppressive ODNs, and then challenged intraarticularly with CpG DNA. The onset and magnitude of the resulting inflammatory response was monitored.


RESULTS
Systemic delivery of CpG ODNs significantly increased susceptibility to local inflammation, whereas systemic treatment with suppressive ODNs reduced this susceptibility. CD11c+ cells played a key role in mediating host sensitivity to arthritis. These cells were the dominant source of tumor necrosis factor alpha production in CpG-stimulated animals and transferred resistance to arthritis from mice treated with suppressive ODNs.


CONCLUSIONS
Systemic exposure to immunostimulatory and immunosuppressive DNA influences host susceptibility to local inflammatory challenge. Current findings raise the possibility that suppressive ODNs may be useful in the prevention/treatment of proinflammatory diseases.
Zeuner
Rainald A
RA
II Medical Clinic, University of Kiel, Kiel, Germany.
Verthelyi
Daniela
D
Gursel
Mayda
M
Ishii
Ken J
KJ
Klinman
Dennis M
DM
D000276:Adjuvants, Immunologic; D019264:Adoptive Transfer; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D016918:Arthritis, Reactive / Q000276:immunology* / Q000473:pathology; D017690:Cell Transplantation; D018899:CpG Islands / Q000276:immunology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D006614:Hindlimb; D007270:Injections, Intra-Articular; D007596:Joints / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000008:administration & dosage / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000276:Adjuvants, Immunologic; D009841:Oligonucleotides; D014409:Tumor Necrosis Factor-alpha