Document Detail


Efficacy of transient treatment with FK506 in the early phase on cyclophosphamide-induced bone marrow chimerism and transplant tolerance across MHC barriers.
MedLine Citation:
PMID:  16376943     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The use of mixed allogeneic bone marrow chimerism to induce donor-specific transplantation tolerance has been extensively demonstrated. In the present study, we assessed the effect of combined use of a short course of FK506 and a single-dose cyclophosphamide (CYP) on the induction of tolerance and development of GVHD after allogeneic BMT. MATERIALS AND METHODS: Lewis rat (RT1(l)) recipients received BMT from Brown Norway (RT1(n)) donors on the next day after injection of CYP at a dose of 200 mg/kg. The recipients were further treated with no FK506 (n = 8), 0.3 mg/kg/day FK506 on days 10-16 (n = 6), or the same dose of FK506 on days 0-6 (n = 6). In a subgroup of animals, heterotopic heart transplantation was performed to investigate transplantation tolerance. RESULTS: Six of eight recipient rats that did not receive FK506 died of severe GVHD, while high levels of chimerism were induced. Recipients of FK506 in the later phase developed mild transient GVHD around 2 to 3 weeks after BMT and recovered thereafter; however, the level of chimerism was significantly decreased (2.8 +/- 2.3% on day 100). Treatment with FK506 in the early phase completely prevented the development of GVHD and induced stable allogeneic chimerism in the long-term (13.8 +/- 8.3% on day 100). These recipients with stable chimerism accepted subsequent BN heart allografts indefinitely (>200 days x 5), while rejecting third-party (BUF) heart allografts by day 12. CONCLUSIONS: Early transient FK506 promotes the induction of stable bone marrow chimerism without GVHD after BMT with CYP pretreatment. The timing of treatment with FK506 is critical with a view to preventing GVHD and inducing stable long-lasting chimerism.
Authors:
Junji Okayama; Saiho Ko; Hiromichi Kanehiro; Hideki Kanokogi; Yoshiyuki Nakajima
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-12-27
Journal Detail:
Title:  The Journal of surgical research     Volume:  133     ISSN:  0022-4804     ISO Abbreviation:  J. Surg. Res.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-29     Completed Date:  2006-07-06     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0376340     Medline TA:  J Surg Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  61-8     Citation Subset:  IM    
Affiliation:
Department of Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Cells / drug effects,  immunology
Cyclophosphamide / pharmacology*
Graft vs Host Disease / drug therapy,  immunology,  prevention & control
Heart Transplantation / immunology
Immunosuppressive Agents / pharmacology*
Lymphocyte Culture Test, Mixed
Major Histocompatibility Complex / immunology*
Rats
Rats, Inbred BN
Rats, Inbred Lew
Survival Rate
Tacrolimus / pharmacology*
Transplantation Chimera / immunology*
Transplantation Tolerance / drug effects*
Transplantation, Homologous / immunology
Chemical
Reg. No./Substance:
0/Immunosuppressive Agents; 109581-93-3/Tacrolimus; 50-18-0/Cyclophosphamide

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