Immunosuppression with a combination of pg490-88 and a subtherapeutic dose of FK506 in a canine renal allograft model.

Abstract

BACKGROUND:

PG490-88 is a water soluble, semisynthetic derivative of a novel compound PG490 (triptolide) purified from the Chinese herb Tripterygium Wilfordii Hook F. In this study, we evaluated the immunosuppressive effect of PG490-88 alone or combined with FK506 in a dog renal transplantation model.

METHODS:

Recipient and donor male beagle dogs were obtained from different breeders to ensure MHC mismatching. PG490-88 and/or FK506 were administered orally based on protocol design.

RESULTS:

All dogs in the untreated group developed acute vascular rejection with a median survival time of 6 days. The grafts from this group presented with massive hemorrhage, IgM, IgG, and C4c deposition. Administration of PG490-88 0.06 mg/kg/day significantly prolonged graft survival to a median survival time of 11 days (P=0.038, vs. control). Treatment with FK506 0.3 mg/kg/day did not prolong graft survival with a median survival time of 9 days. Although FK506 0.6 mg/kg/day significantly prolonged survival, this dose was not tolerated by the dogs. The combination of PG 0.06 mg/kg/day and FK506 0.3 mg/kg/day significantly prolonged survival to a median survival time of 15 days (P=0.017, vs. control). Compared to the untreated control group, the pattern of acute humoral rejection was attenuated in renal allografts treated with PG490-88 and/or FK506. C4c deposition was significantly decreased in renal allografts treated with PG490-88 monotherapy and combination therapy.

CONCLUSIONS:

PG490-88 alone and combined with low dose FK506 significantly prolonged renal allograft survival in a dog model. This agent attenuated acute humoral rejection by inhibiting complement activation and T-cell infiltration.

• Authors: Ximo Wang, Hongtao Sun, Gang Chen, Weihua Liu, Yishai Wise, Chenlin Yung, Yuji Sudo, Kouichi Tamura, Bertha Garcia, Robert Zhong
• Journal: Transplantation (Transplantation) Vol. 79 Issue 11 Pg. 1537-44 (Jun 15 2005) ISSN: 0041-1337 [Print] United States
• PMID: 15940043 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes
• Immunosuppressive Agents
• Triptorelin Pamoate
• Creatinine
• omtriptolide
• Tacrolimus

Topics

• Animals
• Creatinine (blood)
• Diterpenes (therapeutic use)
• Dogs
• Drug Therapy, Combination
• Immunosuppressive Agents (therapeutic use)
• Kidney Transplantation (immunology)
• Monitoring, Physiologic (methods)
• Survival Analysis
• Tacrolimus (therapeutic use)
• Time Factors
• Transplantation, Homologous (immunology)
• Triptorelin Pamoate (therapeutic use)