Organ-specific regulation of pro-inflammatory molecules in heart, lung and kidney following brain death

Brain death and its implications for management of the potential organ donor

“…MHC may increase graft immunogenicity via the T-cell recognition process. 58 In the pig, Skrabal et al 49 found an organspecific regulation of proinflammatory molecules in the kidney, heart, and lung following brain death. Of the cytokines and cytokine-related molecules measured, IL-1b and IL-6 increased in all organs whereas TNF-a only increased in lung tissue.…”

“…These differences may account for differences in organ immunogenicity and may hence contribute to differences in outcome following transplantation. 49 Although the up-regulation of blood cytokines is well documented, the question of origin still remains unclear, and the link(s) between brain death and a systemic inflammatory response may be formed from many sources. 59 Possible sources include affected organs as well as immunocompetent cells in the blood or the damaged brain itself.…”

“…[47][48][49][50] Increased expression of IL-6 and TNF-a has been related to malfunction of donor hearts and prediction of right ventricular failure after human heart transplantation. 51,52 In kidney transplantation, both short-and long-term results of unrelated living transplants are superior to even well-matched cadaveric transplants, [53][54][55] and increased cytokine levels in the blood and kidney of brain-dead donors compared with living donors reflect this difference in outcome between living and cadaveric donation.…”

Early Events in Kidney Donation: Progression of Endothelial Activation, Oxidative Stress and Tubular Injury After Brain Death

“…Under hemodynamic and rheological unstable conditions, endothelial cells have demonstrated their ability to sense variations in mechanical forces, such as shear stress, that appear as a consequence of blood flow and viscosity alterations (4,5). Numerous studies suggest that immune activation with increased endothelial cell activation and immediate early gene expression occurs after BD induction (6)(7)(8)(9). Moreover, the expression of endothelial adhesion molecules ICAM-1 and VCAM-1 and the influx of leukocytes in the kidney are shown to occur faster and be more profound when hemodynamic instability in the brain dead donor is not corrected (10).…”

Lung Diseases - Selected State of the Art Reviews

“…Furthermore, several groups have reported a significant increase in the concentrations of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-2, IL-6, and tumor necrosis factor-alpha (TNFα). (Skrabal et al 2005;Pratschke et al 2000;Shohami et al 1994) Additionally, the neutrophil chemokine, IL-8, has also been demonstrated to be elevated in the lungs of BD lung donors. (Fisher et al 1999) Increased neutrophil burden has been strongly associated with increased matrix-metalloprotease activity and possible exposure of the autoantigen collagen V (Coll V).…”