Distribution and progression of articular lesions in rats treated with 6-sulfanilamidoindazole

Abstract

6-Sulfanilamidoindazole (6SAI)-induced arthritis is one of the models for testing anti-inflammatory agents, and 6SAI induces not only acute arthritis mainly in hindpaws but also systemic inflammation including serositis and arteritis in rats. In this study, in order to clarify the distribution and early progression of articular lesions in this model, we have investigated the detailed pathologic changes in the joints in rats orally administered with 6SAI (500 mg/kg) daily for 7 days or 4 weeks. The articular lesions with similar histopathological changes in nature were systemically noted. In the early phase, mild focal mononuclear cell infiltration was noted in the synovium of joint and/or peritenon, or periarticular connective tissues. The lesions became edematous with infiltration of mononuclear cells and a small number of polymorphonuclear leukocytes and were replaced by granulation tissues later. In the more progressed phase, there were marked fibrosis in the synovium or periarticular tissues along with periosteal new bone formation, while the inflammatory changes mostly disappeared. The marked articular inflammation occurred frequently in tarsal, knee and carpal joints, and mild one in hip joint frequently. The lesions were only sporadically observed in the elbow, shoulder, and vertebrae. No changes were observed in the joints of neck and jaws. The initial changes in the tarsal joints which were most commonly and severely affected were focal monomuclear cell infilatration in the insertions of tendons and/or articular synovium. The present results indicate that 6SAI-induced arthritis may be closely related to physiological load on joints. In addition, it is suggested that the tarsal joint may be the most suitable in assessing anti-inflammatory effects of new agents in this model.