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Lupus, Vol. 17, No. 4, 305-313 (2008)
DOI: 10.1177/0961203307088289
© 2008 SAGE Publications

research-article

Rapamycin prevents the development of nephritis in lupus-prone NZB/W F1 mice

SL Lui

Department of Medicine, The University of Hong Kong, Tung Wah Hospital, Hong Kong SAR, People’s Republic of China; Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, People’s Republic of China

S Yung

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, People’s Republic of China

R Tsang

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, People’s Republic of China

F Zhang

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, People’s Republic of China

KW Chan

Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, People’s Republic of China

S Tam

Department of Clinical Biochemistry, Queen Mary Hospital, Hong Kong SAR, People’s Republic of China

TM Chan

Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, People’s Republic of China

Rapamycin is a potent immunosuppressive drug currently used mainly for rejection prophylaxis in renal transplantation. The aim of this study was to determine the effect of rapamycin treatment on the development of nephritis in lupus-prone New Zealand Black/White F1 (NZB/W F1) mice. Twelve-week-old female NZB/W F1 mice were treated with rapamycin (3 mg/kg body weight) or saline once daily by oral gavage for 20 weeks. The severity of nephritis was assessed by clinical and biochemical parameters, renal histology, immunohistochemistry and gene expression studies. Rapamycin treatment markedly reduced proteinuria, improved renal function, decreased serum anti–double stranded DNA antibody levels and diminished splenomegaly. Kidney sections from saline-treated mice showed marked mesangial proliferation, tubular dilation with protein cast deposition and interstitial inflammatory cell infiltration. Rapamycin-treated mice had near normal renal histology, with marked reduction in glomerular immune deposition and the infiltration by T cells, B cells and macrophages. Rapamycin treatment was associated with down-regulation of intra-renal expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and protein. We conclude that rapamycin is highly effective in preventing the development of nephritis in NZB/W F1 mice. The beneficial effects of rapamycin are mediated through inhibition of lymphoproliferation and reduced MCP-1 expression.

Key Words: autoimmunity • lupus nephritis • NZB/W F1 mice • rapamycin


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