Alteration in progression of murine autoimmune disease by treatment with a novel immunomodulator, SM-8849.

The effects of SM-8849 on the development of autoimmune disease in MRL/Mp-1pr/1pr mice were examined. SM-8849 improved survival as well as renal disease, restored the deficits in splenic cell responsiveness to stimulation by mitogens or conventional antigens, and prevented lymphadenopathy and splenomegaly coincident with a decrease in the number of Thy-1+/Lyt-2-/L3T4- cells. SM-8849 also suppressed the production of the B-cell differentiation factor, possibly with a resulting preferential reduction of autoantibodies. In addition, SM-8849 depressed the production of hydrogen peroxide from macrophages. These results suggest that the administration of SM-8849 to a subject with autoimmune diseases can induce immunological improvements with possible clinical effectiveness.