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CLINICAL RESEARCH: CONGENITAL HEART DISEASE

Intramyocardial synthesis of pro- and anti-inflammatory cytokines in infants with congenital cardiac defects

Ma Qing, MD^*,*, Kathrin Schumacher, MD^*, Ruth Heise, Michael Wöltje, PhD, Jaime F. Vazquez-Jimenez, MD, Thomas Richter, MD, Monika Arranda-Carrero, MD^||, John Hess, MD^*, G.ötz von Bernuth, MD^|| and Marie-Christine Seghaye, MD^*

^* Department of Pediatric Cardiology and Congenital Heart Diseases, German Heart Center Munich, Technical University Munich, Munich, Germany
Interdisciplinary Center for Clinical Research BIOMAT, Aachen University of Technology, Aachen, Germany
Department of Thoracic and Cardiovascular Surgery, Aachen University of Technology, Aachen, Germany
Institute of Pathology, Technical University Munich, Munich, Germany
^|| Department of Pediatric Cardiology, Aachen University of Technology, Aachen, Germany

Manuscript received July 16, 2002; revised manuscript received February 27, 2003, accepted March 20, 2003.

^* Reprint requests and correspondence: Dr. Ma Qing, Department of Pediatric Cardiology and Congenital Heart Diseases, German Heart Center Munich at the Technical University Munich, Lazarettstr. 36, D-80636, Munich, Germany.
ma{at}dhm.mhn.de

OBJECTIVES: We sought to test the hypothesis that cytokines would be expressed in the myocardium of infants with congenital cardiac defects and to identify the signaling pathways involved.

BACKGROUND: Mechanical stress upregulates pro-inflammatory cytokines in the myocardium.

METHODS: Fifteen infants with tetralogy of Fallot (TOF) (n = 7) or with ventricular septal defects (VSDs) (n = 8) were investigated. Concentrations of pro- and anti-inflammatory cytokines and of the inducible nitric oxide synthase (iNOS) were measured by enzyme-linked immunosorbent assay and/or Western blotting in the right ventricular myocardium taken during cardiac surgery. Activation of the nuclear factor-kappa-B (NF-kappa-B) and p38 mitogen-activated protein kinase (MAPK) pathways was assessed by electrophoretic mobility shift assay with supershift and/or Western blotting, respectively.

RESULTS: The pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1-beta, and IL-6 and the anti-inflammatory cytokine IL-10 were detected in the myocardium of all patients. Concentrations of the pro-inflammatory cytokines and also of phosphorylated p38 MAPK were higher in patients with TOF than in those with VSD and correlated with the degree of pressure overload of the right ventricle. Levels of phosphorylated I-kappa-B-alpha, iNOS, and IL-10 were similar in patients with TOF and in those with VSD.

CONCLUSIONS: Our results show intramyocardial synthesis of pro-inflammatory cytokines in infants with congenital cardiac defects. This is associated with activation of both the NF-kappa-B and p38 MAPK pathways. The latter could be particularly important for the transduction of mechanical signals in the infant’s myocardium. Synthesis of IL-10 indicates an intramyocardial anti-inflammatory potential in this age group.

Abbreviations and Acronyms   EMSA = electrophoretic mobility shift assay   IL = interleukin   I-kappa-B = inhibitory kappa-B   iNOS = inducible nitric oxide synthase   LVP = left ventricular pressure   MAPK = mitogen-activated protein kinase   NF-kappa-B = nuclear factor kappa-B   RVP = right ventricular pressure   TNF = tumor necrosis factor   TOF = tetralogy of Fallot   VSD = ventricular septal defect

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