Prolongation of life in female NZB/NZW (F1) hybrid mice by cyclosporin A

Abstract

Oral administration of cyclosporin A (Cy A), an immunosuppressive agent, prolonged the life span of female NZB/NZW (F1) hybrid mice (NZB/W). The most prominent feature of this study was the reduction of glomerular proliferation, proteinurea, and delay of renal failure. Protection from renal damage, in treated mice, occurred despite similar degrees of perivascular cellular infiltration in the kidney and other organs, and glomerular deposition of immunoglobulin and complement. Treatment did not influence the hypergammaglobulinaemia, high levels of circulating immune complexes and later development of autoimmune haemolytic anaemia typically associated with this murine disease. The levels of antibodies to double stranded DNA (dsDNA), an important disease marker, and the response to sheep red blood cells were reduced in the Cy A treated mice, in contrast with the untreated mice. Levels of rheumatoid factors were increased in Cy A treated mice, when compared with untreated mice, and this could play a role in prolongation of life associated with protection from glomerular damage, although it was considered that inhibitory effects on T cell function were a more likely mechanism.