J Korean Soc Plast Reconstr Surg.  1999 Jan;26(1):79-88.

The Effect of FK-506 and Cyclosporine A on Survival of Skin Allograft in Mice

• Jung YH
• Kim SK

Abstract

Cyclosporine A, a fungal metabolite, has been known as a potent immunosuppressant in experimental animals and clinical settings of allotransplantation. It has been responsible for improvements on the success of human kidney, liver, heart, lung, and bone marrow allotransplantation. FK-506, a new antilymphocytic agent, has been reported to be a potent immunosuppressive agent discovered in recent years and now being actively investigated. But there are many questions remaining unanswered about the effective dose and possible side effects of FK-506. So we studied the full thickness skin allotransplantation from BALB/c mouse to C57BL mouse to investigate the survival of allografted skin in a mouse model using the different doses of cyclosporine A and FK-506 and to examine the histological findings at the different period. The results were as follows: 1. The mean survival time (MST) of skin allograft in nontreated control group was 8.6 days. 2. The MST of skin allograft in group 3 treated with cyclosprorine A in 10 mg/kg/day for two weeks was 17.7 days, and that of the group 4 treated with FK-506 in 0.5mg/kg/day for two weeks was 19.7 days. The MST of group 4 was longer than that of group 3 (p>0.05). 3. The MST was increased from 19.7 to 23.1 days as the dose of FK-506 increased from 0.5 mg/kg/day to 1 mg/kg/day (p>0.05). 4. There was no difference in MST between long-term(16 weeks) treatment groups of cyclosporine A and FK-506, and the expire rates of the experimental animals were similarly high in both groups (40%, 50%). 5. The combined treatment of low dose cyclosporine A and FK-506 was more effective method to lengthen the MST and to reduce the expire rate than individual high dose treatment of Cs A or FK-506. 6. The expire rates of experimental animal were higher in long-term treatment groups (36.6%) than in short-term treatment groups(7.5%), and the expire rate of combined treatment groups was lowest (20%) among those of long-term treatment groups. The cause of death was not exactly known, but it could be assumed that the toxicity of drugs may result in death. 7. The histologic findings showed necrosis and mononuclear cell infiltration in rejection period that was consistent with the gross findings, but treated groups maintained normal histological architecture a much longer period than the nontreated group. There was no difference in histologic findings between the cyclosporine A treated groups and FK-506 treated groups. With the above results, it can be concluded that FK-506 and Cs A prolonged the survival of skin allotransplantation in mouse. and the low-dose combined treatment of these two drugs is the most effective method for reducing the rejection. It can be expected that adequate use of these immunosuppressants may be useful for skin allografting in severed burn patients and composite tissue transplantation.

MeSH Terms

Allografts*
Animals
Bone Marrow
Burns
Cause of Death
Cyclosporine*
Heart
Humans
Immunosuppressive Agents
Kidney
Liver
Lung
Mice*
Mice, Inbred C57BL
Necrosis
Skin*
Survival Rate
Tacrolimus*
Tissue Transplantation
Transplantation, Homologous
Transplants
Cyclosporine
Immunosuppressive Agents
Tacrolimus