CYTOKINE MESSENGER-RNA EXPRESSION IN ENDOMYOCARDIAL BIOPSIES DURING ACUTE REJECTION FROM HUMAN HEART-TRANSPLANTS

The immune response to an allograft is regulated by cytokines produced by cells infiltrating the allograft. However, the immunopathogenesis of allograft rejection is not completely understood. To investigate th e role of cytokines after clinical heart transplantation, we analysed the expression of cytokine genes in sequentially taken endomyocardial biopsies (EMB) by using the reverse transcriptase-polymerase chain rea ction (RT-PCR). We analysed 44 EMB from 11 recipients: 21 EMB before o r during rejection, and 23 EMB without histological evidence of acute rejection. A strong correlation was found between IL-2 gene expression and histologically proved rejection (16/21 versus 1/23 without reject ion, P < 0.001; chi(2) test). Also, expression of IL-4 and IL-6 genes was more often found in EMB during rejection than in EMB without signs of rejection (IL-4, 62% versus 35%; and IL-6, 81% versus 39%, respect ively). No relation with rejection or with immunological quiescence wa s observed for the presence of IL-10 gene transcripts. IL-10, but also IL-6 mRNA were detectable in donor heart tissue before transplantatio n (9/10). In contrast, IL-2 and IL-4 gene transcripts were absent in t hese samples. These differences could not be explained by the presence or absence of T cells, since the gene for the constant region of the beta-chain (C beta) of the T cell receptor (TCR) not only was expresse d in post-transplant EMB but also in pretransplant donor heart tissue. Our results provide strong evidence that the immunoregulatory cytokin es IL-2, IL-4 and IL-6 are important local regulators in the graft dur ing acute rejection. The role of IL-10 in the immunologic response to the transplanted organ needs further investigation.