Abstract
Introduction
The action of cortistatin (CST), a novel cyclic neuropeptide, as an anti-inflammatory factor has been studied, but few investigations have explored the immunomodulatory role of CST in transplantation. In the present study, we examined whether CST affects the alloimmune response in a mouse model of skin transplantation and the effects of CST on T lymphocytes.
Methods
BALB/c (H-2Kd) recipient mice (n=70) were divided into seven groups (n=10 per group) and given an intraperitoneal injection of CST or a somatostatin analog, SMS 201-995 (octreotide), on the day of skin transplantation from C57BL/6 (B6) (H-2Kb) donors. Injections were continued for 7 consecutive days. Groups 1-3 received CST at doses of 0.02, 0.2, or 2 mg/kg, respectively. Groups 4–6 received SMS 201–995 at the same doses. Group 7 was a control group and received injections of phosphate buffered saline. Survival of the allografts was recorded. A semiquantitative reverse transcriptase polymerase chain reaction study of Foxp3 expression and a flow cytometry study of CD4 and CD25 markers of T lymphocytes were conducted to determine whether CD4+CD25+ Foxp3high regulatory T cells (Treg) were generated in vivo.
Results
BALB/c mice given CST (0.2 or 2 mg/kg) had prolonged graft survival (median survival time [MST], 13 and 14 days, respectively; P<0.05 compared with controls). SMS 201–995 at the same concentrations did not have a significant effect on allograft survival (MST, 8 days for both groups). We found more than a twofold increase of CD4+CD25+ Treg cells in the CD4+ T-cell population and the expression of Foxp3 was up-regulated in the CST treatment groups, compared with control and SMS 201-995 treatment groups.
Conclusion
In our study, CST induced a significant prolongation in survival time of allogeneic skin grafts and increased the generation of CD4+CD25+ Foxp 3high Treg cells. These results suggest that CST may become a new modality in controlling allograft rejection.
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Wang, J., Zhao, R., Zhang, F. et al. Control of allograft rejection in mice by applying a novel neuropeptide, cortistatin. Adv Therapy 25, 1331–1341 (2008). https://doi.org/10.1007/s12325-008-0121-z
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DOI: https://doi.org/10.1007/s12325-008-0121-z