Expression of cytokine genes in human cardiac allografts: correlation of IL-6 and transforming growth factor-beta (TGF-β) with histological rejection

Abstract

SUMMARY Cytokines may play critical roles in allograft rejection. Currently, a clear pattern of cytokine production that correlates with rejection has not emerged. Our preliminary studies suggested a trend toward increased IL-6 and TGF-β gene expression in cardiac allografts during rejection. We have extended these studies using reverse transcriptase/polymerase chain reaction (RT/PCR) to detect the expression of IL-6. TGF-β, and T cell receptor β chain constant region (TCR-β genes in 21 additional consecutive myocardial biopsies obtained from six heart transplant patients and from five pre-transplant donor hearts. Cytokine gene expression was compared with histological diagnosis of rejection. There was strong correlation between IL-6 as well as TGF-β gene expression, and histological rejection (6/8 biopsies with versus 0/7 without rejection (P = 0·006) and 7/9 biopsies with versus 0/7 without rejection (P=0·003) respectively). Neither IL-6 nor TGF-β transcripts were detected in any pre-transplant donor heart. TCR-β chain mRNA was found in all allograft biopsies regardless of the presence of rejection, but was absent in pre-transplant donor hearts. Our results indicate that expression of IL-6 and TGF-β is highly correlated with allograft rejection and thus may play an important role in regulation of cardiac ailograft rejection. T cell infiltration of allografted myocardium is invariably detected by PCR regardless of histological rejection. The long-term functional significance of these cells in transplanted hearts needs further investigation.