Interleukin 2, interferon, and lymphotoxin in renal transplant recipients

The immunosuppressive action of cyclosporine in transplantation (Tx) is thought to be due to its potent inhibition of lymphokine production by T cells. Several studies have shown a decrease in interleukin 2 (IL-2) and interferon-Gamma (IFN-G) production of renal Tx recipients on CsA treatment and have suggested that increases in lymphokine production can be correlated with rejection episodes. In this study we measured IL-2, IFN-G, and lymphotoxin (LT) production by mitogen-stimulated peripheral blood lymphocytes in eight renal Tx recipients before and at various times after Tx. IL-2 production was significantly (P less than 0.05) decreased by one week post-Tx compared with pre-Tx and normal levels. IFN-G production was significantly (P less than 0.05) decreased by one week post-Tx, after which time it returned to normal. LT production was not decreased post-Tx compared with pre-Tx or normal levels. Lymphokine production was measured every 48-72 hr in the first month post-Tx, when we failed to detect any correlation between increases in production in any of the three lymphokines and rejection episodes. A further group of patients were studied in whom the production of all three lymphokines was measured at the time of diagnosis of rejection and after treatment for rejection. In only 3/5 patients did IL-2 production decrease with a return to stable graft function, while IFN-G production did not alter in these patients. Interestingly LT production increased significantly (P less than 0.05) after treatment. We conclude from these studies that the usefulness of lymphokine determinations for the diagnosis of allograft rejection remains unproved.