Tacrolimus and cyclosporine differ in their capacity to overcome ongoing allograft rejection as a result of their differential abilities to inhibit interleukin-10 production

Transplantation
Hongsi JiangMasakazu Kobayashi

Abstract

Accumulated evidence from clinical transplantation has suggested that tacrolimus-based treatment can reverse ongoing allograft rejection in patients treated with cyclosporine (CsA)-based immunosuppression, even when a high dose of antirejection rescue therapy has failed. This evidence prompted us to investigate whether these two compounds, which share an in vitro mechanism, would differ in their abilities to regulate in situ cellular and molecular events during ongoing allograft rejection. The equivalent effective doses of tacrolimus (3.2 mg/kg/day) and CsA (10 mg/kg/day), when administered orally to Lewis rats for 10 days (day 0-9), were predetermined and defined as the ability of the drug to induce a similar survival of Brown Norway rat heart allografts with an equal suppression of intragraft interleukin (IL)-2 mRNA expression. To investigate the ability of each drug to rescue ongoing allograft rejection, Lewis recipients of Brown Norway rat heart grafts were left untreated for the first 5 days after transplantation. Tacrolimus or CsA was then administered at the equivalent effective dose for 10 days (days 5-14). Heart grafts and blood samples, harvested on days 3, 5, 7, and 10, were analyzed by reverse transcriptase-polymera...Continue Reading

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Citations

Sep 12, 2006·Digestive Diseases and Sciences·Yago Gonzalez-LamaJose Mate
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