Reference : Intrahepatic synthesis of tumor necrosis factor-alpha related to cardiac surgery is inhi...
Scientific journals : Article
Human health sciences : Pediatrics
http://hdl.handle.net/2268/112925
Intrahepatic synthesis of tumor necrosis factor-alpha related to cardiac surgery is inhibited by interleukin-10 via the Janus kinase (Jak)/signal transducers and activator of transcription (STAT) pathway.
English
Qing, Ma [Technische Universität München - TUM > > German Heart Center Munich, Pediatric Cardiology and Congenital Cardiac Diseases > > > >]
Nimmesgern, Ariane [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > Institue of Biochemistry > > > >]
Heinrich, Peter C [Technische Universität München - TUM > > Institue of Biochemistry > > > >]
Schumacher, Kathrin [Technische Universität München - TUM > > > German Heart Center Munich, Pediatric Cardiology and Congenital Cardiac Diseases > > > >]
Vazquez-Jimenez, Jaime F [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > Thoracic and Cardiovascular Surgery > > > >]
Hess, John [Technische Universität München - TUM > > > German Heart Center Munich, Pediatric Cardiology and Congenital Cardiac Diseases > > > >]
von Bernuth, Gotz [Rheinisch - Westfälische Technische Hochschule Aachen - RWTH > > Pediatric Cardiology > > > >]
SEGHAYE, Marie-Christine mailto [Technische Universität München - TUM > > German Heart Center Munich, Pediatric Cardiology and Congenital Cardiac Diseases > > > >]
Dec-2003
Critical Care Medicine
Lippincott Williams & Wilkins
31
12
2769-75
Yes (verified by ORBi)
International
0090-3493
1530-0293
Philadelphia
PA
[en] Animals ; Apoptosis ; Blotting, Western ; Cardiopulmonary Bypass/adverse effects ; Disease Models, Animal ; Electrophoretic Mobility Shift Assay ; Female ; Hypothermia, Induced ; In Situ Nick-End Labeling ; Inflammation ; Interleukin-10/analysis/physiology ; Janus Kinase 1 ; Liver/chemistry/metabolism/pathology ; NF-kappa B/analysis/physiology ; Necrosis ; Protein-Tyrosine Kinases/analysis/physiology ; Proteins/analysis/physiology ; Random Allocation ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Swine ; Tumor Necrosis Factor-alpha/analysis/antagonists & inhibitors/biosynthesis ; Up-Regulation
[en] SUMMARY: OBJECTIVES To identify the signaling pathways involved in the anti-inflammatory shift of the cytokine balance due to hypothermia during cardiopulmonary bypass. DESIGN Experimental animal study. SETTING Department of experimental surgery of a university hospital. SUBJECTS Young pigs. INTERVENTIONS Animals underwent normothermic (37 degrees C) or hypothermic (28 degrees C) cardiopulmonary bypass (n = 6 each). Samples of liver tissue were taken before and 6 hrs after cardiopulmonary bypass. MEASUREMENTS AND MAIN RESULTS Intrahepatic expression of tumor necrosis factor-alpha, interleukin-10, inducible nitric oxide synthase, and suppressor of cytokine signaling-3 was detected by reverse transcriptase polymerase chain reaction and/or Western blotting. Concentrations of the inhibitory protein of nuclear factor-kappaB, IkappaB, and of the signal transducer and activator of transcription (STAT)-3 were measured by Western blotting. The DNA-binding activity of nuclear factor-kappaB and STAT-3 was assessed by electrophoretic mobility shift and supershift assays. Liver cell necrosis and apoptosis were assessed by histology and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay, respectively. Pigs operated on in hypothermia showed significantly higher intrahepatic concentrations of interleukin-10 and lower concentrations of tumor necrosis factor-alpha than the others. They also showed a lower percentage of hepatic cell necrosis but not of apoptosis. This anti-inflammatory reaction observed in the hypothermic group was associated with a higher expression of suppressor of cytokine signaling-3 and with increased activation of STAT-3. Activation of nuclear factor-kappaB and expression of inducible nitric oxide synthase, however, were not significantly different between both groups. CONCLUSION Our results show that hypothermia during cardiopulmonary bypass up-regulates interleukin-10 via STAT-3 activation, which in turn leads to the attenuation of tumor necrosis factor-alpha expression and to hepatic protection.
http://hdl.handle.net/2268/112925
10.1097/01.CCM.0000098858.64868.9C

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