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Updated: Jul 5, 2026
Murine Full-thickness Skin Transplantation
Published on: January 2, 2017
Skin allograft survival and analysis of renal parameters after FTY720 + tacrolimus treatment in mice
C T Lopes1, A P Gallo, P V B Palma
1FAMERP São José do Rio Preto Medical School, São José do Rio Preto, São Paulo, Brazil.
Abstract:
Calcineurin inhibitors such as cyclosporine (CsA) and tacrolimus (FK506) show similar efficacy to prevent rejection within the first year after organ transplantation. However, their use is limited by side effects, such as kidney damage, hypertension, new-onset diabetes, and hyperlipidemia. The consensus opinion suggests that compared with CsA, FK506 has fewer negative effects on blood pressure, serum lipids, and renal function. Nevertheless, FK506 use is associated with a higher incidence of posttransplantation diabetes mellitus. FTY720 is a new compound that has shown beneficial effects in animal models of rejection in transplantation, ischemia/reperfusion injury, autoimmune diseases, and tumor development. Our aim was to investigate whether FTY720 + tacrolimus association could provide additional immunosuppression without causing renal toxicity. FTY720 as a monotherapy or in association with FK506 was administered to C57BL/6 mice for 21 days to prevent skin graft rejection and to evaluate renal function and structure. Increased skin allograft survival in the FTY720 + FK506 group was associated with decreased cell numbers in the spleen, blood, and axillary lymph nodes. Changes in major histocompatibility complex (MHC) class II and intercellular adhesion molecule-1 (ICAM-1) expressions in splenocytes were also found in this group. The major effects already described for FK506 (diabetes) or FTY720 (lymphopenia) were observed after 21 days administration even when the drugs were associated. FTY720 associated with FK506 caused fewer changes in kidney structure, and blood glucose levels were lower than in FK506 monotherapy.
Insights
FTY720 combined with tacrolimus (FK506) enhances immunosuppression for organ transplant patients, reducing kidney damage and blood glucose levels compared to FK506 alone.
Area of Science:
- Immunology
- Pharmacology
- Nephrology
Background:
- Calcineurin inhibitors like tacrolimus (FK506) are effective post-transplant but cause side effects including kidney damage and diabetes.
- FK506 is generally preferred over cyclosporine (CsA) due to fewer effects on blood pressure, lipids, and renal function, but still carries a risk of post-transplant diabetes.
- FTY720 shows promise in preclinical models for various immune-related conditions.
Purpose of the Study:
- To evaluate the efficacy and renal safety of combining FTY720 with tacrolimus (FK506) for immunosuppression.
- To determine if this combination therapy offers enhanced immunosuppression without increasing nephrotoxicity.
Main Methods:
- C57BL/6 mice received FTY720 monotherapy or FTY720 + FK506 for 21 days.
- Skin allograft rejection was monitored.
- Renal function and structure were assessed.
- Splenocyte counts and expression of MHC class II and ICAM-1 were analyzed.
Main Results:
- The FTY720 + FK506 group showed increased skin allograft survival.
- This group also exhibited reduced splenocyte, blood, and lymph node cell counts.
- While expected side effects like lymphopenia (FTY720) and potential for diabetes (FK506) were observed, the combination therapy resulted in fewer kidney structural changes and lower blood glucose levels compared to FK506 monotherapy.
Conclusions:
- FTY720 combined with FK506 provides enhanced immunosuppression.
- This combination demonstrates a potentially improved renal safety profile and better glycemic control compared to FK506 monotherapy.
- Further investigation into FTY720 and FK506 combination therapy is warranted for organ transplantation.
