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Toxicologic Pathology
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Journal Article

Clinical and Histological Assessment of Collagen-Induced Arthritis Progression in the Diabetes-Resistant BB/Wor Rat

Debbie Barney Knoerzer

Department of Immunology, Discovery Research, G. D. Searle and Co., St. Louis, Missouri 63198

Matt G. Donovan

Department of Immunology, Discovery Research, G. D. Searle and Co., St. Louis, Missouri 63198

Benjamin D. Schwartz

Department of Immunology, Discovery Research, G. D. Searle and Co., St. Louis, Missouri 63198

Laurel J. Mengle-Gaw

Department of Immunology, Discovery Research, G. D. Searle and Co., St. Louis, Missouri 63198

Collagen-induced arthritis in the diabetes-resistant BB (DR BB)/Wor rat is a severe, aggressive disease initiated by immunization with heterologous native Type II collagen. Onset of clinical symptoms reproducibly occurs in 100% of animals between days 10 and 12 following collagen immunization. Hypertrophy of the synovial lining is the first histological manifestation of the early inflammatory arthritis. A mild inflammatory infiltrate in the synovium rapidly becomes a fibrovascular pannus eroding articular cartilage and subchondral bone. Beginning at the joint margins, an active synovitis is present. Light microscopy and immunohistochemical staining show the infiltrate to be comprised of mononuclear (lymphocytes, macrophages) and polymorphonuclear inflammatory cells. In addition, there is histological evidence for chronic inflammatory nodules and necrotizing vasculitis in connective tissue from diseased joints, both morphologic features associated with rheumatoid arthritis in humans. Subchondral bone erosion appears to be mediated largely by the resorptive action of activated osteoclasts. These histological parameters of disease progression in the DR BB/Wor rat are similar to human rheumatoid arthritis. The extensive degree of similarity in the pathology of DR BB/Wor rat collagen-induced arthritis and human rheumatoid arthritis supports the role of this model as an in vivo disease model for human rheumatoid arthritis.

Key Words: Rheumatoid arthritis • histopathology • animal model • rheumatoid nodule • necrotizing vasculitis

Toxicologic Pathology, Vol. 25, No. 1, 13-19 (1997)
DOI: 10.1177/019262339702500103
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