Induction of chronic arthritis in rats : the role of intestinal bacteria and bacterial cell wall fragments

Rheumatoid arthritis is a chronic, disabling joint disease occurring in about 1% of the population. Women are more often affected than men, and there is a genetic predisposition based on the presence of the HLA-DR4 (Dw4, Dw14, Dwl5) gene or the HLA-DRl gene. Results from investigations in rheumatoid arthritis patients as well as results from experiments in animal models indicate an imponant role for T helper cells in the disease process. The causative agent in rheumatoid arthritis is not known. In other arthritic diseases (rheumatic fever, reactive arthritis, ankylosing spondylitis) bacterial antigens, often coming from intestinal bacteria, are involved. Also, intestinal diseases can be complicated by arthritic complaints (ulcerative colitis, Crohn's disease, jejunal bypass syndrome). This led to the hypothesis that in rheumatoid anhritis intestinal flora derived antigens may be involved. Evidence supporting this hypothesis comes from studies in which cell wall fragments of aerobic and anaerobic Gram-positive intestinal bacteria are shown to induce arthritis after intraperitoneal injection in rats (intraperitoneal model). Especially Eubacterium aerofaciens cell wall fragments were able to induce a severe chronic arthritis. Histologically the anhritis resembled human rheumatoid anhritis, although also some differences were observed.

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