Organ-specific regulation of pro-inflammatory molecules in heart, lung, and kidney following brain death.
BACKGROUND
Nonspecific inflammatory events following brain death may increase the intensity of the immunological host response. The present study investigated the course of pro-inflammatory molecules in heart, lung, kidney, and plasma after brain death induction.


METHODS
Brain death was induced in five pigs by inflation of an intracranial Foley catheter and five pigs were sham-operated as controls. Each experiment was terminated 6 h after brain death/sham operation and the organs were harvested. We measured the mRNA and protein levels for TNF-alpha, IL-1beta, and IL-6 in heart, lung, kidney, and plasma. Additionally, the mRNA expression for IL-6R, ICAM-1, MCP-1, and TGF-beta was determined in each organ.


RESULTS
After 6 h, the plasma cytokine levels were higher in the brain-dead animals than in the sham-operated. In heart, lung, and kidney there was an increase in IL-6 and IL-1beta following brain death, while TNF-alpha was up-regulated in lung only (P < 0.05). MCP-1 and TGF-beta were significantly higher in heart and lung and IL-6R increased in heart after brain death (P < 0.05).


CONCLUSIONS
Brain death was associated with non-uniform cytokine expression patterns in the investigated organs. These expression patterns may cause variable pro-inflammatory priming resulting in different degrees of damage and explain the organ-specific variation in outcomes after transplantations.
Skrabal
Christian A
CA
Michael E. DeBakey Department of Surgery, Division of Transplant Surgery and Assist Devices, Baylor College of Medicine, Houston, Texas, USA. cskrabal@fastmail.fm
Thompson
Larry O
LO
Potapov
Evgenji V
EV
Southard
Robert E
RE
Joyce
David L
DL
Youker
Keith A
KA
Noon
George P
GP
Loebe
Matthias
M
D000818:Animals; D001926:Brain Death / Q000378:metabolism*; D016207:Cytokines / Q000032:analysis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D007668:Kidney / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000032:analysis; D019947:Receptors, Interleukin-6 / Q000235:genetics; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1