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Rapamycin prevents the development of nephritis in lupus-prone NZB/W F1 mice
1Department of Medicine, The University of Hong Kong, Tung Wah Hospital, Hong Kong SAR, People's Republic of China.
Abstract:
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.
Insights
Rapamycin effectively prevents nephritis in lupus-prone mice by inhibiting immune cell proliferation and reducing inflammation. This study shows rapamycin
Area of Science:
- Immunology
- Nephrology
- Pharmacology
Background:
- Rapamycin is an immunosuppressive drug used in transplantation.
- Systemic lupus erythematosus (SLE) can cause lupus nephritis.
- NZB/W F1 mice are a model for human lupus and nephritis.
Purpose of the Study:
- To investigate the therapeutic potential of rapamycin in preventing nephritis development in lupus-prone NZB/W F1 mice.
- To assess the impact of rapamycin on clinical, biochemical, histological, and molecular markers of nephritis.
Main Methods:
- NZB/W F1 mice received daily oral rapamycin (3 mg/kg) or saline for 20 weeks.
- Nephritis severity was evaluated using clinical assessments, blood tests, renal histology, immunohistochemistry, and gene expression analysis.
- Key parameters included proteinuria, renal function, autoantibodies, splenomegaly, glomerular pathology, immune cell infiltration, and MCP-1 expression.
Main Results:
- Rapamycin treatment significantly reduced proteinuria, improved renal function, and decreased serum anti-dsDNA antibodies.
- Histological analysis revealed near-normal kidney architecture in rapamycin-treated mice, with reduced glomerular immune deposits and inflammatory cell infiltration.
- Rapamycin administration led to down-regulation of intra-renal monocyte chemoattractant protein-1 (MCP-1) mRNA and protein expression.
Conclusions:
- Rapamycin demonstrates high efficacy in preventing the development of nephritis in NZB/W F1 mice.
- The therapeutic benefits are attributed to the inhibition of lymphoproliferation and reduced MCP-1 expression.
- Rapamycin holds promise as a treatment strategy for lupus nephritis.
