Intraportal delivery of immunosuppression to intrahepatic islet allograft recipients

X. Wang, E. J. Alfrey, A. Posselt, L. Tafra, A. M. Alak, D. C. Dafoe

Research output: Contribution to journalArticlepeer-review

Abstract

Local delivery of immunosuppressive agents may dampen local alloreactive events with avoidance of systemic toxicity. We investigated the innovative strategy of intraportal (IPO) delivery of three immunosuppressive agents in streptozotocin diabetic rat recipients of islet allografts (Lewis to Wistar-Furth) transplanted intrahepatically. IPO budesonide (BUD, 240 or 360 μg/kg per day), a potent steroid, and cyclosporin (CyA, 2 or 4 mg/kg per day) did not prolong graft mean survival time [MST±standard deviation (SD)] as compared to nonimmunosuppressed recipients. Fourteen days of IPO FK 506 (0.16 mg/kg per day) significantly increased MST as compared with untreated controls (49±29 vs 7±1 days, P<0.01) and was more effective than intravenous (IV) FK 506 (17±7 days, P<0.01). When FK 506 was given for 28 days, the benefit of IPO over IV delivery was reaffirmed (MST 81±32 vs 34±4 days, P<0.01). The potential for toxicity was lessened by lower mean systemic levels in the IPO group as compared to the IV group (1.3±0.6 vs 3.5±0.9 ng/mg, P<0.02). The strategy of continuous IPO FK 506 was effective in the prevention of rejection of intrahepatic islet allografts.

Original languageEnglish (US)
Pages (from-to)268-272
Number of pages5
JournalTransplant International
Volume8
Issue number4
DOIs
StatePublished - Jul 1 1995

Keywords

  • Budesonide
  • FK 506
  • Immunosuppression
  • Islet allografts
  • islet allografts
  • local

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'Intraportal delivery of immunosuppression to intrahepatic islet allograft recipients'. Together they form a unique fingerprint.

Cite this