The Journal of Heart and Lung Transplantation
Volume 27, Issue 3 , Pages 317-324, March 2008

Myocardial Pro-inflammatory Cytokine Expression and Cellular Rejection in Pediatric Heart Transplant Recipients

  • John P. Breinholt, MD

      Affiliations

    • Department of Pediatrics (Cardiology), Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
    • Corresponding Author InformationReprint requests: John P. Breinholt, MD, Department of Pediatrics, Section of Pediatric Cardiology, Indiana University School of Medicine, 702 Barnhill Drive, Rm 127, Indianapolis, IN 46202. Telephone: 317-274-8906. Fax: 317-274-4022.
    • ,
  • Jesus G. Vallejo, MD

      Affiliations

    • Department of Pediatrics (Cardiology), Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
    • ,
  • Corey M. Gates, RN

      Affiliations

    • Department of Pediatrics (Cardiology), Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
    • ,
  • Sarah K. Clunie, RN

      Affiliations

    • Department of Pediatrics (Cardiology), Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
    • ,
  • Debra L. Kearney, MD

      Affiliations

    • Department of Pathology, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
    • ,
  • William J. Dreyer, MD

      Affiliations

    • Department of Pediatrics (Cardiology), Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
    • ,
  • Jeffrey A. Towbin, MD

      Affiliations

    • Department of Pediatrics (Cardiology), Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas
    • Department of Molecular and Human Genetics, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas.
    • ,
  • Neil E. Bowles, PhD

      Affiliations

    • Department of Pediatrics (Cardiology), Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas

Received 24 October 2007; received in revised form 6 December 2007; accepted 13 December 2007.

Background

Accumulating evidence suggests that immune-mediated injury is important in the development of rejection after heart transplantation. We hypothesized that pro-inflammatory cytokine expression would increase in biopsy samples that manifest cellular rejection and that this would correlate with the development and progression of transplant cellular rejection.

Methods

Children with heart transplants were prospectively enrolled from July 2004 to November 2005. Right ventricular endomyocardial biopsies were obtained during routine catheterization for rejection surveillance. Cellular rejection was graded using criteria established by the International Society for Heart and Lung Transplantation. RNA was extracted from biopsy samples and reverse transcription was used for complementary DNA synthesis. The cDNA product was evaluated by quantitative real-time polymerase chain reaction (PCR) to measure the following cytokines: interleukin (IL)-1β, IL-6 and IL-18; tumor necrosis factor-alpha (TNF-α); and interferon-gamma (IFN-γ). Normalized cytokine mRNA transcripts were correlated with cellular rejection scores and the presence of viral genome.

Results

Seventy-four children (mean age 9.6 ± 5.5 years, range 0.2 to 20.5 years) were enrolled and 95 biopsies were obtained. None of the cytokines demonstrated a correlation with the cellular rejection score, even within individual patients for whom multiple, serial biopsy samples were studied. Eighteen biopsy samples were found to have parvovirus B19 genome present, but there was no correlation between cytokine levels and the presence of parvovirus.

Conclusions

Cytokine transcripts in heart transplants do not correlate with cellular rejection. In addition, there is no correlation between cytokine transcripts and the presence of viral genome.

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 Supported by the National Institutes of Child Health and Human Development, Pediatric Scientist Development Program (Grant Award K12-HD00850 to J.P.B., J.A.T.); the Abby Glaser Children’s Heart Fund (J.A.T.); and the Texas Children’s Foundation Chair in Pediatric Cardiac Research (J.A.T.).

 Present affiliation for Dr Bowles: Department of Pediatrics, University of Utah School of Medicine, Eccles Institute of Human Genetics, Salt Lake City, Utah.

PII: S1053-2498(07)01520-3

doi:10.1016/j.healun.2007.12.002

The Journal of Heart and Lung Transplantation
Volume 27, Issue 3 , Pages 317-324, March 2008

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