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

Prolonged lifespan and high incidence of neoplasms in NZB/NZW mice treated with hydrocortisone sodium succinate. This study investigated the effects of prolonged corticosteriod 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. Allongement de la duree de vie et grande frequence des neoplasies chez les souris NZB/NZW traitees par l'hydrocortisone (succinate sodique). Ce travail etudie les effets de la corticotherapie prolongee sur l'evolution de l'affection autoimmune spontanee et de la cancerisation chez les souris NZB/NZW, un modele animal de lupus erythemateux. Vingt jeunes souris femelles NZB/NZW ont ete traitees jusqu'a leur mort par des doses faibles de succinate sodique d'hydrocortisone (3,3 mg/kg/jour) et 21 souris ont recu des fortes doses (10 mg/kg/jour). Quinze souris controles ont recu du solute sale. Le traitement au long cours avec Tune ou l'autre des doses a effectivement limite la maladie renale et allonge la duree de vie. Cinquante six pour cent des animaux recevant la dose faible ont developpe des cancers et 38% des souris de ce groupe sont mortes d'une atteinte renale. Les cancers ont determine la mort de 76% des souris recevant une dose elevee. Le traitement au long cours a ete associe a une predominance des sarcomes, qui sont apparus chez les souris âgees. Des etudes anterieures de ce laboratoire avaient demontre une augmentation de la duree de vie au moyen du traitement par le cyclophosphamide des souris NZB/NZW. Quatre vingt dix sept pour cent des souris traitees par le cyclophosphamide developpent des neoplasies, surtout des lymphomes ou des carcinomes. Il est conclu que les neoplasies surviennent chez les souris NZB/NZW âgees dont la vie a ete prolongee par les drogues immunosuppressives ou antiinflammatoires. Le traitement specifique employe dans chacune des etudes a cependant influence le type de neoplasie.