Methylprednisolone therapy in deceased donors reduces inflammation in the donor liver and improves outcome after liver transplantation: a prospective randomized controlled trial.
OBJECTIVE
To investigate potential beneficial effects of donor treatment with methylprednisolone on organ function and outcome after liver transplantation.


BACKGROUND
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-alpha, and inducible protein-10 was observed. Methylprednisolone treatment resulted in a significant downregulation of intercellular adhesion molecule-1, tumor necrosis factor-alpha, 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.
Kotsch
Katja
K
Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
Ulrich
Frank
F
Reutzel-Selke
Anja
A
Pascher
Andreas
A
Faber
W
W
Warnick
P
P
Hoffman
S
S
Francuski
M
M
Kunert
C
C
Kuecuek
O
O
Schumacher
G
G
Wesslau
C
C
Lun
A
A
Kohler
S
S
Weiss
S
S
Tullius
S G
SG
Neuhaus
P
P
Pratschke
Johann
J
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001926:Brain Death / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000097:blood; D005260:Female; D006801:Humans; D007249:Inflammation / Q000453:epidemiology / Q000517:prevention & control; D007376:Interleukin-2 / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins / Q000097:blood; D008099:Liver / Q000276:immunology; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D011184:Postoperative Period; D011446:Prospective Studies; D015427:Reperfusion Injury / Q000453:epidemiology / Q000276:immunology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D000893:Anti-Inflammatory Agents; D018932:Chemokine CCL2; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D008775:Methylprednisolone