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Methylprednisolone Therapy in Deceased Donors Reduces Inflammation in the Donor Liver and Improves Outcome After Liver Transplantation

2008; Lippincott Williams & Wilkins; Volume: 248; Issue: 6 Linguagem: Inglês

10.1097/sla.0b013e318190e70c

1528-1140

Katja Kotsch, Frank Ulrich, Anja Reutzel‐Selke, Andreas Pascher, Wladimir Faber, Peter Warnick, S. Hoffman, M. Francuski, C. Kunert, O Kuecuek, Guido Schumacher, C Wesslau, Andreas Lun, Sven Köhler, Sascha Weiß, Stefan G. Tullius, P. Neuhaus, Johann Pratschke,

Neurological Complications and Syndromes

In Brief Objective: To investigate potential beneficial effects of donor treatment with methylprednisolone on organ function and outcome after liver transplantation. Summary Background Data: It is proven experimentally and clinically that the brain death of the donor leads to increased levels of inflammatory cytokines and is followed by an intensified ischemia/reperfusion injury after organ transplantation. In experiments, donor treatment with steroids successfully diminished these effects and led to better organ function after transplantation. Methods: To investigate whether methylprednisolone treatment of the deceased donor is applicable to attenuate brain death-associated damage in clinical liver transplantation we conducted a prospective randomized treatment-versus-control study in 100 deceased donors. Donor treatment (n = 50) consisted of 250 mg methylprednisolone at the time of consent for organ donation and a subsequent infusion of 100 mg/h until recovery of organs. A liver biopsy was taken immediately after laparotomy and blood samples were obtained after brain death diagnosis and before organ recovery. Cytokines were assessed by real-time reverse transcriptase-polymerase chain reaction. Soluble serum cytokines were measured by cytometric bead array system. Results: After methylprednisolone treatment, steroid plasma levels were significantly higher (P < 0.05), and a significant decrease in soluble interleukins, monocyte chemotactic protein-1, interleukin-2, interleukin-6, tumor necrosis factor-α, and inducible protein-10 was observed. Methylprednisolone treatment resulted in a significant downregulation of intercellular adhesion molecule-1, tumor necrosis factor-α, major histocompatibility complex class II, Fas-ligand, inducible protein-10, and CD68 intragraft mRNA expression. Significantly ameliorated ischemia/reperfusion injury in the posttransplant course was accompanied by a decreased incidence of acute rejection. Conclusions: Our present study verifies the protective effect of methylprednisolone treatment in deceased donor liver transplantation, suggesting it as a potential therapeutical approach. This prospective randomized study demonstrates that brain dead-induced proinflammatory changes in the donor can be substantially reversed after treatment with methylprednisolone. Donor treatment leads to reduced immunogenicity before transplantation, a decreased ischemia/reperfusion injury, and improved organ function after transplantation.