Local production of cytokines in the human cardiac allograft. A sequential study.

The observations of 2 types of CD4+ T cells (Th1 and Th2), which can be distinguished by their different cytokine profiles, has led to the possibility that analysis of cytokine profiles produced locally within transplanted allografts could be predictive of rejection or acceptance of that graft. We have investigated the expression of IL-2 and TNF beta (Th1 type cytokines), IL-4 and IL-10 (Th2 type cytokines), and the proinflammatory cytokines TNF alpha and IL-1 beta in sequential endomyocardial biopsies collected from 12 cardiac transplant recipients during the first 4 months after transplantation, by the analysis of RNA extracted from each biopsy by reverse transcriptase-polymerase chain reaction. The results obtained were compared with histopathological and clinical indicators of rejection. IL-2 was found in all severe (grade 3), in 57% of moderate (grade 2), in 21% of mild (grade 1) rejection, and in only 1 nonrejection (subsequently progressing to grade 3), where rejection was classified by routine histology. IL-4 and IL-10 were absent from grade 3 rejection, but present in 24% (IL-4) and in 17% (IL-10) of mild rejection and in a single nonrejecting biopsy, respectively. IL-4 was found in 2 cases of moderate rejection, and IL-10 in 1 case of moderate rejection. Statistical analysis showed that the presence of IL-2 positively correlated with both mild and moderate rejection, while IL-4 correlated with mild rejection (P < or = 0.05). IL-1 beta, TNF alpha, and TNF beta were found in both rejecting and nonrejecting biopsies, with no significant differences between the histological grades. Our results suggest that in the human situation, IL-2 and IL-4 may indeed be important in the modulation of rejection.