Targeting inflammatory responses in the brain dead donor

Bo Liu

Targeting inflammatory responses in the brain dead donor

Bo Liu

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Hersendode donoren zijn de meest voorkomende bron voor niertransplantatie hetgeen de beste therapie is voor eindstadium nierziekte. Hersendood (BD) is een complex proces waarbij een ontstekingsreactie leidt tot verslechterde transplantaatfunctie. Onze groep vond datprednisolon toediening voor BD, in tegenstelling tot toediening na BD een verminderde renale ontsteking oplevert. Het neutraliseren van IL-6 of TNF-a,, beide inflammatoire cytokines leverde bij toediening van bindende anti lichamen voorafgaand aan BD geenverbeterde nierfunctie op als we verwacht hadden. We speculeren dat IL-6 en TNF-a zowel pro- en anti-inflammatoire werking heeft die beide via een relatief onafhankelijk signaal transductie pathway de ontstekingsreactie mediëren, hoewel ze overlap en interactievertonen. Het is mogelijk dat een meer selectieve blokkade van de schadelijke functie met behoud van enkele gunstige functies een betere methode kan zijn om de onstekingsreactie bij hersendood te remmen. In de toekomst zal de nadruk liggen op selectieve targeting en immunosuppressieve inductie therapie om de opbrengst van donororganen te optimaliseren en de uitkomst in de ontvanger te verbeteren.

Originele taal-2	English
Kwalificatie	Doctor of Philosophy
Toekennende instantie	Rijksuniversiteit Groningen
Begeleider(s)/adviseur	Leuvenink, Henri, Supervisor Zhang, Jian-ning, Supervisor, Externe Persoon
Datum van toekenning	17-feb.-2016
Plaats van publicatie	[Groningen]
Uitgever	University of Groningen
Gedrukte ISBN's	978-90-367-8475-7
Elektronische ISBN's	978-90-367-8474-0
Status	Published - 2016

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Title and contens Final publisher's version, 861 KB
Chapter 1Final publisher's version, 2,78 MB
Chapter 2 Final publisher's version, 5,71 MB
Chapter 3Final publisher's version, 6,13 MB
Chapter 4Final publisher's version, 4,98 MB
Chapter 5Final publisher's version, 3,42 MB
Chapter 6Final publisher's version, 2,73 MB
Chapter 7Final publisher's version, 3,11 MB
AppendicesFinal publisher's version, 2,66 MB
Complete thesisFinal publisher's version, 19,3 MB
PropositionsFinal publisher's version, 26,6 KB

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title = "Targeting inflammatory responses in the brain dead donor",

abstract = "Brain dead donors are the most common source for renal transplantation as the best therapy to treat end-stage kidney disease. Brain death (BD) is a complex pathological process, causing an inflammatory response which results in inferior graft function. Our group found prednisolone administration before BD, instead of after BD reduced renal inflammation. Unfortunately, neutralizing IL-6 or TNF-a, both central and pleiotropic inflammatory cytokines prior to BD did not improve renal function as we expected. We speculate that IL-6 and TNF-a possess both pro- and anti-inflammatory effect, meanwhile they have relatively independent signaling transduction pathway mediating the inflammatory response, even though they are overlapped and interacted. Therefore, the best way could be selective blockage of the detrimental feature while maintaining some beneficial function intact. In the future, focus will be on selective targeting and induction immunosuppressive therapy to maximize the yield of donor organs and improve receipt outcome.",

author = "Bo Liu",

year = "2016",

language = "English",

isbn = "978-90-367-8475-7",

publisher = "University of Groningen",

school = "University of Groningen",

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T1 - Targeting inflammatory responses in the brain dead donor

AU - Liu, Bo

PY - 2016

Y1 - 2016

N2 - Brain dead donors are the most common source for renal transplantation as the best therapy to treat end-stage kidney disease. Brain death (BD) is a complex pathological process, causing an inflammatory response which results in inferior graft function. Our group found prednisolone administration before BD, instead of after BD reduced renal inflammation. Unfortunately, neutralizing IL-6 or TNF-a, both central and pleiotropic inflammatory cytokines prior to BD did not improve renal function as we expected. We speculate that IL-6 and TNF-a possess both pro- and anti-inflammatory effect, meanwhile they have relatively independent signaling transduction pathway mediating the inflammatory response, even though they are overlapped and interacted. Therefore, the best way could be selective blockage of the detrimental feature while maintaining some beneficial function intact. In the future, focus will be on selective targeting and induction immunosuppressive therapy to maximize the yield of donor organs and improve receipt outcome.

AB - Brain dead donors are the most common source for renal transplantation as the best therapy to treat end-stage kidney disease. Brain death (BD) is a complex pathological process, causing an inflammatory response which results in inferior graft function. Our group found prednisolone administration before BD, instead of after BD reduced renal inflammation. Unfortunately, neutralizing IL-6 or TNF-a, both central and pleiotropic inflammatory cytokines prior to BD did not improve renal function as we expected. We speculate that IL-6 and TNF-a possess both pro- and anti-inflammatory effect, meanwhile they have relatively independent signaling transduction pathway mediating the inflammatory response, even though they are overlapped and interacted. Therefore, the best way could be selective blockage of the detrimental feature while maintaining some beneficial function intact. In the future, focus will be on selective targeting and induction immunosuppressive therapy to maximize the yield of donor organs and improve receipt outcome.

M3 - Thesis fully internal (DIV)

SN - 978-90-367-8475-7

PB - University of Groningen

CY - [Groningen]

ER -

Targeting inflammatory responses in the brain dead donor

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