Significant reduction of proinflammatory cytokines by treatment of the brain-dead donor.
BACKGROUND
Experimental studies suggest that brain death in the donor has a significant impact on graft quality; however, there are no data correlating organ-specific cytokine expression and the corresponding serum protein levels in human organ donors. Furthermore, it is unknown whether donor treatment can reduce the up-regulation of proinflammatory cytokines and thereby optimize organ quality.


METHODS
We investigated the expression pattern of cytokines comparing serum (n = 53) and tissue expression (n = 25) in brain-dead human donors. The controls were living donors (n = 25). Additionally 41 deceased donors were treated with steroids before organ harvest (250 mg initial, afterward 100 mg/h until laparotomy). Hepatic tissue samples were obtained immediately after donor laparotomy to assess transcription rates of tissue cytokines (IL-6, IL-10, CD3, TGFb, TNFa, BAG, HO-1, Mipla) by RT-PCR. Serum samples were obtained after declaration of brain death and before laparotomy.


RESULTS
Transcription of proinflammatory cytokines was significantly increased in brain-dead compared to living donor grafts (P < .005). Donor treatment with steroids led to significantly decreased tissue and serum expression of proinflammatory cytokines (P < .01), which were comparable to living donors. Tissue levels of cytokines (IL-6, IL-10) correlated strongly with serum levels of the corresponding proteins.


CONCLUSIONS
Serum protein levels of proinflammatory cytokines proffer a valuable, easy accessible marker to define the immunological status of a graft. Our data suggest a beneficial effect of anti-inflammatory treatment of brain-dead organ donors.
Kuecuek
O
O
Deutsche Stiftung Organtransplantation, DSO Berlin-Brandenburg, Berlin, Germany.
Mantouvalou
L
L
Klemz
R
R
Kotsch
K
K
Volk
H D
HD
Jonas
S
S
Wesslau
C
C
Tullius
S
S
Neuhaus
P
P
Pratschke
J
J
D001926:Brain Death; D016207:Cytokines / Q000187:drug effects / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006498:Hepatectomy; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013256:Steroids / Q000494:pharmacology; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting; D014158:Transcription, Genetic
D016207:Cytokines; D013256:Steroids