Prolonged lifespan and high incidence of neoplasms in NZB/NZW mice treated with hydrocortisone sodium succinate.

This study investigated the effects of prolonged corticosteroid therapy on the course of spontaneous autoimmune disease and oncogenesis in NZB/NZW mice, an animal model of systemic lupus erythematosus. Twenty young female NZB/NZW mice were treated until death with low-dose hydrocortisone sodium succinate (3.3 mg/kg/day), and 21 mice received high-dose hydrocortisone (10 mg/kg/day). Fifteen control mice were injected with saline. Long-term therapy with either dose of hydrocortisone effectively prevented renal disease and prolonged lifespans in NZB/NZW mice. Fifty-six percent of low-dose treated animals developed neoplasms, and 38% of mice in this treatment group died with renal disease. Neoplasms caused death in 76% of mice receiving high-dose treatment. Long-term hydrocortisone therapy was associated with a predominance of sarcomas, which appeared in aged mice after a long period of treatment. In earlier studies conducted in this laboratory, cyclophosphamide treatment prolonged life in NZB/NZW mice. Ninety-seven percent of cyclophosphamide-treated mice developed neoplasms; most tumors were lymphomas or carcinomas. It was concluded that neoplasms occur commonly in old NZB/NZW mice with lives prolonged by immunosuppressive or antiinflammatory drugs. Nevertheless, the specific therapeutic agent used in each study influenced the types of neoplasms appearing in treated mice.