Cytokine mRNA expression in peripheral blood cells of immunosuppressed human islet transplant recipients

The macrophage derived cytokines interleukin-l beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha), and the T-cell derived cytokine interfer on gamma (IFN gamma) have been implicated to play an important role in earl y attack on islet cells during human islet transplantation (ITx). Therefore , the aim of this study was to investigate the influence of the current imm unosuppressive induction therapy in clinical islet transplantation on mRNA expression of these cytokines in blood cells, compared to lipopolysaccharid e (LPS) induced cytokine release in vitro and to plasma levels. The cytokin e release correlated to lymphocyte counts and significantly decreased after ATG, and partially recovered 2 weeks after ITx. Unexpectedly, there was no correlation between mRNA expression for IL-1 beta in total blood and the n umber of lymphocytes and monocytes remaining after anti thymocyte globulin (ATG)-therapy. Even when the blood was nearly totally depleted from mononuc lear cells, high amounts of IL-1 beta mRNA could be detected. However, IL-1 beta secretion could not be stimulated in vitro. Our results show that app lication of ATG during ITx might contribute to graft survival during the ea rly posttransplant period by suppression of the synthesis of monocyte deriv ed cytokines IL-1 beta and TNF alpha.