HILDA LIF, G-CSF, IL-1-BETA, IL-6, AND TNF-ALPHA PRODUCTION DURING ACUTE REJECTION OF HUMAN KIDNEY ALLOGRAFTS

HILDA/LIF, a recently described glycoprotein, has been characterized from supernatants of alloreactive T cell clones (CD4 and CD8) extracted from a human rejected kidney graft. This suggests a possible role for HILDA/LIF in the rejection process. In order to further investigate this possible role and the role of other cytokines in allograft rejection, we tested HILDA/LIF, G.CSF, IL-6, TNF alpha, and IL-1 beta in supernatants of cultured mononucleated cells from patients during rejection and from stable grafted patients. In addition, we also tested HILDA/LIF in urine of the same patients. No significant differences were directly observed in the production of HILDA/LIF, TNF alpha, and IL-1 beta in supernatants from mononucleated cells between rejecting and stable patients. However, when antibodies were used to block the TNF alpha and the IL-1 beta receptors, an increase of both cytokines was detected in cells from rejecting patients suggesting that an over-expression of both receptors and cytokines occurred during rejection. A significant increase was also observed for both G.CSF and IL-6 during the rejection compared to stable grafts. In addition, HILDA/LIF was detected in urine of patients during rejection and not in urine of stable patients, suggesting that this cytokine may indeed play a role in rejection.