LOW-LEVEL OF INTERLEUKIN-10 SYNTHESIS DURING LIVER ALLOGRAFT-REJECTION

Interleukin 10 (IL-10) is a macrophage and T-cell-derived cytokine wit h potent immunosuppressive properties. To assess its role in liver all ograft rejection, we evaluated the plasma level and in situ production of IL-10 after liver transplantation and designed in vitro studies to asses the effects of IL-10 on the allogeneic response. Normal control s and liver transplant recipients with acute rejection, chronic reject ion, other complications (recurrent hepatitis C, biliary complications ), or no complications were evaluated. The plasma IL-10 level was meas ured by an immunoenzymatic technique. IL-10 expression in the liver wa s detected on frozen liver biopsies by in situ hybridization and immun ohistochemistry. Plasma IL-10 levels were not elevated during acute or chronic rejection, when compared with liver recipients with uncomplic ated transplants. IL-10 mRNA and protein expressions in the liver graf t were restricted to rare scattered sinusoidal cells of transplant rec ipients with acute or chronic rejection, as well as in those with no c omplications. In mixed lymphocyte cultures performed with peripheral b lood mononuclear cells (PBMC) from normal subjects, IL-10 decreased th e cell proliferation in a dose-dependent manner, and this immunosuppre ssion was synergistic with that of cyclosporine or FK506. These findin gs indicate that IL-10 production is low during allograft rejection. T hus, IL-10 therapy in association with cyclosporine or FK506 might be proposed after liver transplantation.