PMID- 20808264
OWN - NLM
STAT- MEDLINE
DCOM- 20101116
LR  - 20131121
IS  - 1534-6080 (Electronic)
IS  - 0041-1337 (Linking)
VI  - 90
IP  - 8
DP  - 2010 Oct 27
TI  - Effects of pravastatin on murine chronic graft-versus-host disease.
PG  - 853-60
LID - 10.1097/TP.0b013e3181f2c92b [doi]
AB  - 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.
FAU - Yoon, Hyoung-Kyu
AU  - Yoon HK
AD  - Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
FAU - Lim, Ji-Young
AU  - Lim JY
FAU - Kim, Tae-Jung
AU  - Kim TJ
FAU - Cho, Chul-Soo
AU  - Cho CS
FAU - Min, Chang-Ki
AU  - Min CK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Transplantation
JT  - Transplantation
JID - 0132144
RN  - 0 (Chemokines)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Minor Histocompatibility Antigens)
RN  - KXO2KT9N0G (Pravastatin)
SB  - IM
MH  - Animals
MH  - Chemokines/analysis
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Graft vs Host Disease/*etiology/immunology/pathology
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred Strains
MH  - Minor Histocompatibility Antigens/immunology
MH  - Pravastatin/*therapeutic use
MH  - Skin Transplantation/immunology/pathology
MH  - Transplantation, Isogeneic
EDAT- 2010/09/03 06:00
MHDA- 2010/11/17 06:00
CRDT- 2010/09/03 06:00
PHST- 2010/09/03 06:00 [entrez]
PHST- 2010/09/03 06:00 [pubmed]
PHST- 2010/11/17 06:00 [medline]
AID - 10.1097/TP.0b013e3181f2c92b [doi]
PST - ppublish
SO  - Transplantation. 2010 Oct 27;90(8):853-60. doi: 10.1097/TP.0b013e3181f2c92b.