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.
Qing, Ma; Nimmesgern, Ariane; Heinrich, Peter Cet al.
2003 • In Critical Care Medicine, 31 (12), p. 2769-75
[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.
Disciplines :
Pediatrics
Author, co-author :
Qing, Ma; Technische Universität München - TUM > German Heart Center Munich, Pediatric Cardiology and Congenital Cardiac Diseases
SEGHAYE, Marie-Christine ; Technische Universität München - TUM > German Heart Center Munich, Pediatric Cardiology and Congenital Cardiac Diseases
Language :
English
Title :
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.
Publication date :
December 2003
Journal title :
Critical Care Medicine
ISSN :
0090-3493
eISSN :
1530-0293
Publisher :
Lippincott Williams & Wilkins, Philadelphia, United States - Pennsylvania
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