Experimental arthropathy induced in rhesus monkeys (Macaca mulatta) by intradermal immunization with native bovine type II collagen.

Over a 6-month time course, polyarticular arthritis was induced in 7 male rhesus monkeys by 3 intradermal injections of bovine type II collagen emulsified in complete Freund's adjuvant, followed later by 2 intradermal injections of type II collagen in incomplete Freund's adjuvant. All animals exhibited delayed-type hypersensitivity to type II collagen by skin test and had serum anti-type II collagen titers of greater than 10,000 (at 1 month) and 20,000 to 160,000 (at 6 months) by enzyme-linked immunosorbent assay. Gross joint changes were observed in 6 of 7 monkeys, especially in the knee and elbow; synovial cell hyperplasia, increased vascularization and a focal mononuclear cell infiltrate were the most frequent findings. Chronic arthritis with destructive cartilage lesions was most prominent in the phalangeal joints of the hands (7 of 7 animals). Microscopically, these changes consisted of fibrosis of the synovium with increased vascularization, villous synovial membrane hyperplasia and focal mononuclear cell infiltration, as well as fibrous metaplasia of the articular cartilage adjacent to pannus formations. Also evident was a loss of safranin O staining intensity in the cartilage and loss of continuity of the articular surface. The 7 control monkeys (received Freund's adjuvant without collagen) were delayed-type hypersensitivity-negative, had no serum anti-type II collagen antibodies, and had grossly and microscopically normal joints. This primate model resembles collagen-induced arthritis seen in rodents and, to some degree, human rheumatoid arthritis.