CLINICAL AND HISTOLOGICAL ASSESSMENT OF COLLAGEN-INDUCED ARTHRITIS PROGRESSION IN THE DIABETES-RESISTANT BB WOR RAT/

Collagen-induced arthritis in the diabetes-resistant BE (DR BB)/Wor ra t is a severe, aggressive disease initiated by immunization with heter ologous native Type II collagen. Onset of clinical symptoms reproducib ly occurs in 100% of animals between days 10 and 12 following collagen immunization. Hypertrophy of the synovial lining is the first histolo gical manifestation of the early inflammatory arthritis. A mild inflam matory infiltrate in the synovium, rapidly becomes a fibrovascular pan nus eroding articular cartilage and subchondral bone. Beginning at the joint margins, an active synovitis is present. Light microscopy and i mmunohistochemical staining show the infiltrate to be comprised of mon onuclear (lymphocytes, macrophages) and polymorphonuclear inflammatory cells. In addition, there is histological evidence for chronic inflam matory nodules and necrotizing vasculitis in connective tissue from di seased joints, both morphologic features associated with rheumatoid ar thritis in humans. Subchondral bone erosion appears to be mediated lar gely by the resorptive action of activated osteoclasts. These histolog ical parameters of disease progression in the DR BB/Wor rat are simila r to human rheumatoid arthritis. The extensive degree of similarity in the pathology of DR BB/Wor rat collagen-induced arthritis and human r heumatoid arthritis supports the role of this model as an in vivo dise ase model for human rheumatoid arthritis.