PMID- 27473158
OWN - NLM
STAT- MEDLINE
DCOM- 20170330
LR  - 20211204
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 39
IP  - 5
DP  - 2016 Oct
TI  - Modulation of Immunologic Response by Preventive Everolimus Application in a Rat 
      CPB Model.
PG  - 1771-82
LID - 10.1007/s10753-016-0412-5 [doi]
AB  - Everolimus (EVL) is widely used in solid organ transplantation. It is known to 
      have antiproliferative and immunosuppressive abilities via inhibition of the mTOR 
      pathway. Preventive EVL administration may lower inflammation induced by 
      cardiopulmonary bypass (CPB) and reduce systemic inflammatory response syndrome 
      (SIRS). After oral loading with EVL 2.5 mg/kg/day (n = 11) or placebo (n = 11) 
      for seven consecutive days, male Wistar rats (400-500 g) were connected to a 
      miniaturised heart-lung-machine performing a deep hypothermic circulatory arrest 
      protocol. White blood cells (WBC) were significantly reduced in EVL-pretreated 
      animals before start of CPB with a preserved reduction by trend at all other time 
      points. Ischemia/reperfusion led to decreased glucose levels. Application of EVL 
      significantly increased glucose levels after reperfusion. In addition, potassium 
      levels were significantly lower in EVL-treated animals at the end of reperfusion. 
      Immunoblotting revealed increased S6 levels after CPB. EVL decreased 
      phosphorylation of S6 in the heart and kidney, which indicates an inhibition of 
      mTOR pathway. Moreover, EVL significantly modified phosphorylation of AKT, while 
      decreasing IL2, IL6, RANTES, and TNFalpha (n = 6). Preventive application of EVL may 
      modulate inflammation by inhibition of mammalian target of rapamycin (mTOR) 
      pathway and reduction of proinflammatory cytokines. This may be beneficial to 
      evade SIRS-related morbidities after CPB.
FAU - Pinto, Antonio
AU  - Pinto A
AD  - Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University 
      Medical School, Moorenstrasse 5, 40225, Duesseldorf, Germany.
FAU - Jahn, Annika
AU  - Jahn A
AD  - Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University 
      Medical School, Moorenstrasse 5, 40225, Duesseldorf, Germany.
FAU - Immohr, Moritz Benjamin
AU  - Immohr MB
AD  - Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University 
      Medical School, Moorenstrasse 5, 40225, Duesseldorf, Germany.
FAU - Jenke, Alexander
AU  - Jenke A
AD  - Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University 
      Medical School, Moorenstrasse 5, 40225, Duesseldorf, Germany.
FAU - Dohrn, Laura
AU  - Dohrn L
AD  - Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University 
      Medical School, Moorenstrasse 5, 40225, Duesseldorf, Germany.
FAU - Kornfeld, Markus
AU  - Kornfeld M
AD  - Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University 
      Medical School, Moorenstrasse 5, 40225, Duesseldorf, Germany.
FAU - Lichtenberg, Artur
AU  - Lichtenberg A
AD  - Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University 
      Medical School, Moorenstrasse 5, 40225, Duesseldorf, Germany.
FAU - Akhyari, Payam
AU  - Akhyari P
AD  - Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University 
      Medical School, Moorenstrasse 5, 40225, Duesseldorf, Germany. 
      payam.akhyari@med.uni-duesseldorf.de.
FAU - Boeken, Udo
AU  - Boeken U
AD  - Department of Cardiovascular Surgery, Medical Faculty, Heinrich-Heine-University 
      Medical School, Moorenstrasse 5, 40225, Duesseldorf, Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Cytokines)
RN  - 0 (Immunosuppressive Agents)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cardiopulmonary Bypass/adverse effects
MH  - Cytokines/metabolism
MH  - Everolimus/administration & dosage/*pharmacology
MH  - Immunosuppressive Agents/pharmacology
MH  - Inflammation/drug therapy
MH  - Male
MH  - Metabolic Networks and Pathways/drug effects
MH  - Models, Animal
MH  - Premedication
MH  - Rats
MH  - Rats, Wistar
MH  - Reperfusion Injury/prevention & control
MH  - Systemic Inflammatory Response Syndrome/prevention & control
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - cardiopulmonary bypass
OT  - cytokine
OT  - deep hypothermic cardiac arrest
OT  - everolimus
OT  - ischemia
OT  - reperfusion
OT  - systemic inflammatory syndrome
EDAT- 2016/07/31 06:00
MHDA- 2017/03/31 06:00
CRDT- 2016/07/31 06:00
PHST- 2016/07/31 06:00 [entrez]
PHST- 2016/07/31 06:00 [pubmed]
PHST- 2017/03/31 06:00 [medline]
AID - 10.1007/s10753-016-0412-5 [pii]
AID - 10.1007/s10753-016-0412-5 [doi]
PST - ppublish
SO  - Inflammation. 2016 Oct;39(5):1771-82. doi: 10.1007/s10753-016-0412-5.