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)-1beta, IL-6 and IL-18; tumor necrosis factor-alpha (TNF-alpha); and interferon-gamma (IFN-gamma). 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.
Breinholt
John P
JP
Department of Pediatrics (Cardiology), Baylor College of Medicine and Texas Children's Hospital, Houston, Texas, USA. jpbreinh@iupui.edu
Vallejo
Jesus G
JG
Gates
Corey M
CM
Clunie
Sarah K
SK
Kearney
Debra L
DL
Dreyer
William J
WJ
Towbin
Jeffrey A
JA
Bowles
Neil E
NE
D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism*; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology*; D006321:Heart / Q000821:virology; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology*; D010322:Parvoviridae Infections; D016732:Parvovirus B19, Human / Q000235:genetics; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; D004279:DNA, Viral; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma