Significant reduction of proinflammatory cytokines by treatment of the brain-dead donor.

INTRODUCTION

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.