Intra-articularly localized bacterial DNA containing CpG motifs induces arthritis

Unmethylated CpG motifs are often found in bacterial DNA, and exert immunos timulatory effects on hematopoetic cells(1-3). Bacteria produce severe join t inflammation in septic and reactive arthritides; bacterial DNA may be inv olved in this process. We injected bacterial DNA originating from Escherich ia coli and Staphylococcus aureus and oligonucleotides containing CpG direc tly into the knee joints of mice of different strains. Arthritis Nas seen b y histopathology within 2 hours and lasted for at east 14 days. Unmethylate d CpG motifs were responsible for this induction of arthritis, as oligonucl eotides containing these motifs produced the arthritis. The arthritis was c haracterized by an influx of monocytic, Mac-1(+) cells and by a lack of T l ymphocytes. Depletion of monocytes resulted in abrogation of the synovial i nflammation. Tumor necrosis factor (TNF)-alpha, a cytokine produced by cell s of the monocyte/macrophage lineage, is an important mediator of this dise ase, as expression of mRNA for TNF-alpha was evident in the inflamed joints , and the CpG-mediated inflammation was abrogated in mice genetically unabl e to produce this cytokine. These findings demonstrate that bacterial DNA c ontaining unmethylated CpG motifs induces arthritis, and indicate an import ant pathogenic role for bacterial DNA in septic arthritis.