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Updated: Jun 9, 2026
Induction of Graft-versus-host Disease and In Vivo T Cell Monitoring Using an MHC-matched Murine Model
Published on: August 29, 2012
Effects of pravastatin on murine chronic graft-versus-host disease
Hyoung-Kyu Yoon1, Ji-Young Lim, Tae-Jung Kim
1Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Insights
Pravastatin (PST) treatment slowed chronic graft-versus-host disease (CGVHD) onset and reduced skin fibrosis and inflammation in a mouse model. This suggests PST may be a potential therapy for CGVHD by down-regulating chemokines and collagen synthesis.
Area of Science:
- Immunology
- Transplantation Medicine
- Pharmacology
Background:
- Chronic graft-versus-host disease (CGVHD) is a significant complication of allogeneic hematopoietic stem-cell transplantation with limited effective therapies.
- Statins have shown efficacy in immune-mediated diseases, but their role in CGVHD is undetermined.
Purpose of the Study:
- To investigate the therapeutic effect of statins, specifically pravastatin (PST), on the development of CGVHD.
- To evaluate PST's impact on CGVHD-related pathology and immune cell infiltration.
Main Methods:
- A B10.D2→BALB/c mouse model of CGVHD was utilized.
- Pravastatin (30 mg/kg/day) was administered intraperitoneally for 4 weeks post-transplantation.
Main Results:
- PST treatment significantly delayed the onset of clinical cutaneous CGVHD and reduced skin pathologic changes.
- PST attenuated lung submucosal fibrosis, collagen deposition in skin and lungs, and inflammatory cell counts in bronchoalveolar lavage fluid.
- PST reduced donor CD11b and CD4 cell infiltration and decreased levels of MCP-1 and RANTES in affected tissues.
Conclusions:
- Pravastatin demonstrates a protective effect against CGVHD in a murine model.
- The mechanism involves down-regulation of chemokines and reduction of collagen synthesis, suggesting PST as a potential CGVHD therapeutic agent.
Background:
Chronic graft-versus-host disease (CGVHD) is a serious and increasingly common complication after allogeneic (allo) hematopoietic stem-cell transplantation, but currently available therapies have demonstrated limited efficacy. Furthermore, the statins have been reported to be effective in various immune-mediated disease models, but their therapeutic potentials versus CGVHD have not been determined.
Methods:
We used a B10.D2→BALB/c model of CGVHD, which differs at minor histocompatibility loci, to address the therapeutic effect of statins on the development of CGVHD. Pravastatin (PST, 30 mg/kg/day) was intraperitoneally injected for 5 days per week from the day of transplantation until 4 weeks after allo hematopoietic stem-cell transplantation.
Results:
The onset of clinical cutaneous GVHD was significantly slower in PST-treated recipients than in allo-controls (36 days vs. 25 days, respectively, P<0.05), and pathologic changes in skin disease confirmed this clinical result. Animals injected with PST showed less submucosal fibrosis in lungs than allo-controls. In addition, collagen deposition in skin and lungs was markedly attenuated by PST treatment. PST also significantly reduced protein concentrations and numbers of inflammatory and epithelial cells in bronchoalveolar lavage fluid. Significantly lower numbers of donor CD11b and CD4, but not CD8 cells, were observed in skin and bronchoalveolar lavage fluid after PST treatment. The protein concentrations of monocyte chemoattractant protein-1 (MCP-1) and regulated on activation normal T cell expressed and secreted (RANTES) in skin and lungs were substantially reduced in PST-treated animals when compared with allo-controls.
Conclusions:
This study suggests that the CGVHD-protecting effect of PST involves the down-regulation of chemokines and the reduction of collagen synthesis.
