Prevention of lupus diseases in MRL/1, NZBxNZW, and BXSB mice treated with a cyclophosphazene derived drug.

A polyclonal activation of lymphocytes (PA) has been suggested to play a pathogenic role in autoimmune and immune complex diseases, particularly in mouse lupus. "DIAM 4," a cyclophosphazene derived drug, selected on the basis of its ability to modulate a PA has been used to treat female MRL/1, female NZBxNZW, and male BXSB mice. In these three strains of mice, the treatment was found to induce an inhibition of the PA, to prevent the increase of anti-DNA antibody levels and the simultaneous decrease of C3 levels, to prevent the appearance of proteinuria, the deposition of immune complexes in glomeruli, and the development of kidney lesions. Moreover in MRL/1 mice, lymphoproliferation was prevented. These results suggest that drugs able to modulate a PA might be efficient in the treatment of mouse lupus nephritis. Such a principle of immunomodulation might open the way to new possibilities of treatment of lupus and other immune complex diseases.