Reduction of CpG-induced arthritis by suppressive oligodeoxynucleotides.
OBJECTIVE
Bacterial DNA contains immunostimulatory CpG motifs that cause inflammation when injected into the knee joints of normal mice. We examined whether synthetic oligodeoxynucleotides (ODN) that suppress CpG-induced immune responses prevent CpG-induced arthritis.


METHODS
CpG, suppressive, and/or control ODN were injected into the knees of BALB/c mice. Joint swelling and inflammation were evaluated by physical measurement, by histologic analysis of joint tissue, and by magnetic resonance imaging.


RESULTS
Immunostimulatory CpG DNA induced local arthritis, characterized by swelling of the knee joints, the presence of inflammatory cell infiltrates, the perivascular accumulation of mononuclear cells, and hyperplasia of the synovial lining. Administering suppressive (but not control) ODN reduced the manifestations and severity of arthritis up to 80%.


CONCLUSIONS
Suppressive ODN may be useful for the prevention or treatment of arthritis induced by bacterial DNA.
Zeuner
Rainald A
RA
Center for Biologics Evaluation and Research, FDA, Bethesda, Maryland, and Christian-Albrechts-University Kiel, Kiel, Germany.
Ishii
Ken J
KJ
Lizak
Martin J
MJ
Gursel
Ihsan
I
Yamada
Hiroshi
H
Klinman
Dennis M
DM
Verthelyi
Daniela
D
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D016918:Arthritis, Reactive / Q000188:drug therapy*; D018899:CpG Islands; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D007270:Injections, Intra-Articular; D007719:Knee Joint / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D009841:Oligonucleotides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha