The features of arthritis induced by CpG motifs in bacterial DNA

Objective. To investigate the features of arthritis induced by bacterial DN A that contain CpG motifs. Methods. Bacterial DNA originating from Escherichia coli and Staphylococcus aureus or synthetic oligonucleotides containing CpG motifs were injected d irectly into knee joints of mice. Histopathologic joint damage, antibody le vels, cytokine levels, and synovial messenger RNA (mRNA) expression of cyto kines and chemokines were assessed. Results. Histopathologic signs of arthritis were evident within 2 hours and lasted for at least 3 weeks. Nonmethylated CpG motifs were responsible for the induction of arthritis since oligonucleotides containing these motifs triggered arthritis, whereas methylation of these nucleotides abrogated the inflammatory response. Arthritis was characterized by an influx of monocyt ic, Mac-1+ cells and by a scarcity of T lymphocytes, The disease was charac terized locally by mRNA expression of macrophage-derived cytokines (tumor n ecrosis factor alpha, interleukin-12 [IL-12], IL-1 beta) and chemokines (mo nocyte chemoattractant protein 1, RANTES) in arthritic joints. Systemically , the arthritis was characterized by increased levels of circulating IL-6 a nd immunoglobulins. Conclusion. These findings demonstrate that bacterial DNA that contain nonm ethylated CpG motifs induces arthritis, suggesting an important pathogenic role for bacterial DNA in septic arthritis.