6-Sulfanilamidoindazole (6SAI) is a sulfonamide that induces acute. self-limiting arthritis in rats, and 6SAI-induced arthritis is thought to be a model for testing anti-inflammatory agents. In this study, in order to clarify the location of arthritis and relationships between arthritis and other changes in this model, we have investigated the detailed pathologic changes in rats administered orally with 6SAI (125, 250, 500 rngkg) daily for 4 wk in a time-course experiment. hloderate to severe arthritis was observed in rats of middle-and high-dose groups. Histologically, in the affected ankle. exudative synovitis and periarthritis tvcrc observed at 1 wk, granulation tissue formation with angiogenesis and pcriosteal new bone formation at 2 wk, and marked fibrosis of affected area at 4 wk. respectively. In addition to these changes, in pcriarticular and pcnosteal tissues of affected ankles, subendothelial insudation of small-sized arteries and medial fibrinoid degeneration of medium-sized arteries were observed at 1 and 2 wk and intimal thickening and medial hypertrophy at 4 wk, rcspcctivcly. No arterial changes were observed in the unaffected ankles. Similar arterial changes were often observed in the liver, thyroid glands, and lungs and rarely in various organs and tissues. Acute inflammation of serous tissues such as mesentery, mediastinum, and capsule of spleen or thymus \ v e x also present in 6SAI-treated groups, and it was sometimes accompanied by arteritis. In addition, in 6SAI-treated rats, follicular hypcrplasia of thyroid glands and pituitary changes, which arc thought to be related to depression of thyroid hormone production by 6SAI. were observed. These results show that 6SAIinduces not only arthritis but also arteritis. serositis. and thyroid change. and it is necessary to take the interaction between these changes into consideration when anti-inflammatory agents are tested in this model. Subendothelial insudation; medial fibrinoid degeneration; intimal thickening; medial hypertrophy; serositis; thyroid K e y o r d s . follicular hyperplasia
