Immune Netw.  2003 Jun;3(2):150-155. 10.4110/in.2003.3.2.150.

Effects of Cyclosporin A, FK506, and 3-Deazaadenosine on Acute Graft-versus-host Disease and Survival in Allogeneic Murine Hematopoietic Stem Cell Transplantation

• Jin JY
• Jeong DC
• Eom HS
• Chung NG
• Park SJ
• Choi BO
• Min WS
• Kim HK
• Kim CC
• Han CW

• KMID: 2150581
• DOI: http://doi.org/10.4110/in.2003.3.2.150

Abstract

BACKGROUND
We investigated the effect of donor marrow T cell depletion, administration of FK506, cyclosporin A (CSA), and 3-deazaadenosine (DZA) on graft versus host disease (GVHD) after allogeneic murine hematopoietic stem cell transplantation (HSCT). METHODS: We used 4 to 6 week old Balb/c (H-2(d), recipient), and C3H/He (H-2(k), donor) mice. Total body irradiated recipients received 1x10(7) bone marrow cells (BM) and 0.5x10(7) splenocytes of donor under FK506 (36 mg/kg/day), CSA (5 mg/kg/day, 20 mg/kg/day), and DZA (45 mg/kg/day), which were injected intraperitoneally from day 1 to day 14 daily and then three times a week for another 2 weeks. To prevent the GVHD, irradiated Balb/c mice were transplanted with 1x10(7) rotor-off (R/O) cells of donor BM. The severity of GVHD was assessed daily by clinical scoring method. RESULTS: All experimental groups were well grafted after HSCT. Mice in experimental group showed higher GVHD score and more rapid progression of GVHD than the mice with R/O cells (R/O group) (p<0.01). There were relatively low GVHD scores and slow progressions in FK506 and low dose CSAgroups than high dose CSA group (p<0.01). The survival was better in FK506 group than low dose CSA group. All mice treated with CSA died within 12 days after HSCT. The GVHD score in DZA group was low and slow in comparison with control group (p<0.05), but severity and progression were similar with low dose CSA group (p=0.11). All mice without immunosuppressive treatment died within 8 days, but all survived in R/O group (p<0.01). Survival in low dose CSA group was longer than in control group (p<0.05), but in high dose CSA group, survival was similar to control group. The survival benefit in DZA group was similar with low dose CSA group. FK506 group has the best survival benefit than other groups (p<0.01), comparable with R/O group (p=0.18), although probability of survival was 60%. CONCLUSION: We developed lethal GVHD model after allogeneic murine HSCT. In this model, immunosuppressive agents showed survival benefits in prevention of GVHD. DZA showed similar survival benefits to low dose CSA. We propose that DZA can be used as a new immunosuppressive agent to prevent GVHD after allogeneic HSCT.

Keyword

3-Deazaadenosine; graft versus host disease; allogeneic murine hematopoietic stem cell transplantation

MeSH Terms

Animals
Bone Marrow
Bone Marrow Cells
Cyclosporine*
Graft vs Host Disease*
Hematopoietic Stem Cell Transplantation*
Hematopoietic Stem Cells*
Humans
Immunosuppressive Agents
Mice
Research Design
Tacrolimus*
Tissue Donors
Transplants
Cyclosporine
Immunosuppressive Agents
Tacrolimus