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

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.