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Early Renal Ischemia‐Reperfusion Injury in Humans Is Dominated by IL‐6 Release from the Allograft
Author(s) -
De Vries D. K.,
Lindeman J. H. N.,
Tsikas D.,
De Heer E.,
Roos A.,
De Fijter J. W.,
Baranski A. G.,
Van Pelt J.,
Schaapherder A. F. M.
Publication year - 2009
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2009.02675.x
Subject(s) - medicine , pathophysiology , ischemia , kidney , transplantation , reperfusion injury , acute kidney injury , kidney transplantation , complement system , renal ischemia , renal function , endothelial activation , immunology , inflammation , pharmacology , antibody
The pathophysiology of ischemia/reperfusion (I/R) injury is complex, and current knowledge of I/R injury in humans is incomplete. In the present study, human living‐donor kidney transplantation was used as a highly reproducible model to systematically study various processes potentially involved in early I/R injury. Unique, direct measurements of arteriovenous concentration differences over the kidney revealed massive release of interleukin (IL)‐6 in the first 30 minutes of graft reperfusion and a modest release of IL‐8. Among the assessed markers of oxidative and nitrosative stress, only 15( S )‐8‐ iso ‐PGF 2α was released. When assessing cell activation, release of prothrombin factor 1 + 2 indicated thrombocyte activation, whereas there was no release of markers for endothelial activation or neutrophil activation. Common complement activation complex sC5b‐9 was not released into the bloodstream, but was released into urine rapidly after reperfusion. To investigate whether IL‐6 plays a modulating role in I/R injury, a mouse experiment of renal I/R injury was performed. Neutralizing anti‐IL‐6 antibody treatment considerably worsened kidney function. In conclusion, this study shows that renal I/R in humans is dominated by local IL‐6 release. Neutralization of IL‐6 in mice resulted in a significant aggravation of renal I/R injury.