New model of a synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine- induced arthritis: clinical and histologic studies in athymic nude and euthymic rats.

A synthetic adjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), induced severe polyarthritis in euthymic rnu/+ rats. The rnu/+ rats were the most susceptible to MDP-induced arthritis among various rat strains tested, whereas congenitally athymic nude rats (rnu/rnu), males or females, did not develop the disease. This disease was clinically and histologically indistinguishable from classic adjuvant-induced arthritis in terms of clinical course, clinical signs, and histologic features such as (1) an initial acute exudative reaction observed primarily in stroma of the synovial membrane, periarticular tissue, about the tendons, tendon sheath, along the periosteum, between muscle bundles and in the subcutaneous tissue; (2) hypertrophy of the synovial villi, hyperplasia of the synovial lining cells; (3) the very active periosteal new bone formation; and (4) granulation tissue growth either in the articular tissues or in liver, lymph nodes, and capsule of the spleen. Thus, it is postulated that MDP-induced arthritis is basically the same disease as classic adjuvant-induced arthritis. The thymus may play an important role in promoting the development of the disease, possibly through some immune mechanisms to undetermined antigen(s). We believe that nonimmune mechanisms may also be involved in some part of acute and chronic inflammatory reactions to MDP molecules. This new model of MDP-induced arthritis will be a very useful tool to elucidate the underlying mechanisms of adjuvant-induced arthritis.