Skin Allograft Survival and Analysis of Renal Parameters After FTY720 + Tacrolimus Treatment in Mice

Lopes, Camila Takáo; Gallo, Ana Paula; Palma, Patrícia Viana Bonini; Cury, Patrí­cia Maluf; Bueno, Valquíria

doi:10.1016/j.transproceed.2008.02.051

Cited by 14 publications

(14 citation statements)

References 22 publications

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“…Several studies have shown that FTY720 given in combination with tacrolimus caused a synergistic effect in rat allograft models, such as skin, cardiac, liver and kidney transplantation (Xu et al 1998;Tamura et al 2000;Gallo et al 2006;Lopes et al 2008). In this study it was found that treatment with combination of FTY720 and tacrolimus had a significantly stronger effect on promoting functional recovery of spinal cord damage than treatment with either FTY720 or tacrolimus alone.…”

Section: Discussionmentioning

confidence: 52%

“…Moreover, the unique mechanism of FTY720 allows for its use in combination with other immunosuppressants (Tamura et al 2000). In fact, the combination of FTY720 and tacrolimus produced additional immunosuppressive effects in rat allograft models (Hoshino et al 1999;Tamura et al 2000) and resulted in fewer changes in kidney structure and lower blood glucose levels than did tacrolimus alone (Gallo et al 2006;Lopes et al 2008). The present study investigated whether the combination of FTY720 and tacrolimus could result in a synergistic and beneficial effect on functional recovery after SCI.…”

mentioning

confidence: 99%

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Treatment with Immunosuppressants FTY720 and Tacrolimus Promotes Functional Recovery after Spinal Cord Injury in Rats

Zhang

Sun

et al. 2009

Tohoku J. Exp. Med.

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Section: Discussionmentioning

confidence: 52%

mentioning

confidence: 99%

Treatment with Immunosuppressants FTY720 and Tacrolimus Promotes Functional Recovery after Spinal Cord Injury in Rats

Zhang

Sun

et al. 2009

Tohoku J. Exp. Med.

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“…Previously, fingolimod has been successfully combined with immunosuppressive treatments, such as steroids, to prevent transplant rejection. 42,43 The data support that fingolimod represents an excellent candidate for acute therapy of autoimmune disease. However, the effectiveness of our treatment protocol for patients with uveitis, or indeed other autoimmune diseases, remains to be tested with or without concomitant standard immunosuppressive therapy.…”

Section: Commentmentioning

confidence: 77%

Fingolimod (FTY720) as an Acute Rescue Therapy for Intraocular Inflammatory Disease

Raveney¹,

Copland²,

Nicholson³

et al. 2008

Archives of Ophthalmology

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“…In 2008, we demonstrated that the increased skin allograft survival in FTY720-treated mice was associated with diminished cell numbers in the spleen, blood and axillary lymph nodes (24). Our present results showed a reduction in the number of cells and percentage of CD4 + Foxp3 + cells in the lymph nodes of mice treated with FTY720.…”

Section: Discussionmentioning

confidence: 99%

The imbalance between Treg and Th17 cells caused by FTY720 treatment in skin allograft rejection

Commodaro¹,

Pedregosa²,

Peron³

et al. 2012

Clinics

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OBJECTIVES:FTY720 modulates CD4+T cells by the augmentation of regulatory T cell activity, secretion of suppressive cytokines and suppression of IL-17 secretion by Th17 cells. To further understand the process of graft rejection/acceptance, we evaluated skin allograft survival and associated events after FTY720 treatment.METHODS:F1 mice (C57BL/6xBALB/c) and C57BL/6 mice were used as donors for and recipients of skin transplantation, respectively. The recipients were transplanted and either not treated or treated with FTY720 by gavage for 21 days to evaluate the allograft survival. In another set of experiments, the immunological evaluation was performed five days post-transplantation. The spleens, axillary lymph nodes and skin allografts of the recipient mice were harvested for phenotyping (flow cytometry), gene expression (real-time PCR) and cytokine (Bio-Plex) analysis.RESULTS:The FTY720 treatment significantly increased skin allograft survival, reduced the number of cells in the lymph nodes and decreased the percentage of Tregs at this site in the C57BL/6 recipients. Moreover, the treatment reduced the number of graft-infiltrating cells and the percentage of CD4+ graft-infiltrating cells. The cytokine analysis (splenocytes) showed decreased levels of IL-10, IL-6 and IL-17 in the FTY720-treated mice. We also observed a decrease in the IL-10, IL-6 and IL-23 mRNA levels, as well as an increase in the IL-27 mRNA levels, in the splenocytes of the treated group. The FTY720-treated mice exhibited increased mRNA levels of IL-10, IL-27 and IL-23 in the skin graft.CONCLUSIONS:Our results demonstrated prolonged but not indefinite skin allograft survival by FTY720 treatment. This finding indicates that the drug did not prevent the imbalance between Tr1 and Th17 cells in the graft that led to rejection.

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Skin Allograft Survival and Analysis of Renal Parameters After FTY720 + Tacrolimus Treatment in Mice

Cited by 14 publications

References 22 publications

Treatment with Immunosuppressants FTY720 and Tacrolimus Promotes Functional Recovery after Spinal Cord Injury in Rats

Treatment with Immunosuppressants FTY720 and Tacrolimus Promotes Functional Recovery after Spinal Cord Injury in Rats

Fingolimod (FTY720) as an Acute Rescue Therapy for Intraocular Inflammatory Disease

The imbalance between Treg and Th17 cells caused by FTY720 treatment in skin allograft rejection

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