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Prevention of murine lupus disease in (NZBxNZW)F1 mice by sirolimus treatment

Department of Nephrology, Universitary Hospital "Marqués de Valdecilla', Santander, Spain, marabarron{at}wanadoo.es

C. Piñera-Haces

Department of Nephrology, Universitary Hospital "Marqués de Valdecilla', Santander, Spain

C. Gómez-Alamillo

Department of Nephrology, Universitary Hospital "Marqués de Valdecilla', Santander, Spain

I. Santiuste-Torcida

Department of Nephrology, Universitary Hospital "Marqués de Valdecilla', Santander, Spain

J.C. Ruiz

Department of Nephrology, Universitary Hospital "Marqués de Valdecilla', Santander, Spain

L. Buelta-Carrillo

Department of Medical and Surgical Sciences, "Universidad de Cantabria', Santander, Spain

R. Merino

Department of Molecular Biology, "Universidad de Cantabria", associated to "Centro de Invetigaciones Biológicas/Consejo Superior de Investigaciones Científicas", Santander, Spain

Á.L.M. de Francisco

Department of Nephrology, Universitary Hospital "Marqués de Valdecilla', Santander, Spain

M. Arias

Department of Nephrology, Universitary Hospital "Marqués de Valdecilla', Santander, Spain

Sirolimus is a new immunosuppressive drug used to avoid allograft rejection. The immunosuppressive effect of sirolimus is due to inhibition of the mammalian target of rapamycin, necessary for the proliferation and clonal expansion of activated T-cells. Because T-cells play a central role in the pathogenesis of autoimmune disease developed in (NZBxNZW)F1 mice, we evaluated the therapeutic use of sirolimus in such mice. (NZBxNZW)F1 female mice received 1mg/kg/day of sirolimus from 12 to 37 weeks of age. The development of autoimmune disease was evaluated by measuring the serum levels of auto-antibodies (autoAbs) and their immunoglobulin isotypes, prevalence of glomerulonephritis and mortality rates. Sirolimus directly inhibited production of autoAbs, glomerular deposits of immunoglobulins and development of proteinuria; also the survival of these mice was prolonged. Our results demonstrate the beneficial effects of sirolimus in preventing the development of lupus disease in (NZBxNZW)F1 female mice. Lupus (2007) 16, 775—781.

Key Words: auto-antibodies • (NZBxNZW)F1 mice • proteinuria • sirolimus • systemic lupus erythematosus

Lupus, Vol. 16, No. 10, 775-781 (2007)
DOI: 10.1177/0961203307081401


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