SYSTEMIC RELEASE OF INTERLEUKIN-10 DURING ORTHOTOPIC LIVER-TRANSPLANTATION

Experimental and clinical observations indicate that the liver allogra ft is less immunogenic than other organ transplants and can promote im mune tolerance. Because interleukin-10 recently emerged as a macro pha ge and T-cell-derived cytokine with potent immunosuppressive propertie s, we studied its production in 28 patients undergoing orthotopic live r transplantation. Plasma levels of immunoreactive interleukin-10 dram atically increased within 2 hr after liver allograft reperfusion, with peak levels ranging between 214 and 4998 pg/ml (median = 677 pg/ml). This systemic release of interleukin-10 was transient because it retur ned to low levels by 48 hr (range = 26 to 51 pg/ml). The higher interl eukin-10 levels measured in right atrial blood as compared with portal blood indicated that interleukin-10 was most likely synthesized withi n the liver graft. To get insight into the cellular origin of interleu kin-10, we also measured serum levels of interleukin-4 and interferon- gamma, both produced by T cells, and interleukin-8, a cytokine secrete d by macrophages, in eight patients. Interleukin-4 and interferon-gamm a levels remained undetectable in most of the patients, whereas interl eukin-8 levels paralleled those of interleukin-10. Portal endotoxemia was probably not involved in interleukin-10 production because endotox in levels remained low (<20 pg/ml) before and after liver allograft re perfusion. Interleukin-10 plasma levels did not correlate either with cold ischemia time or with the occurrence of rejection episodes. We co nclude that orthotopic liver transplantation is associated with a mass ive release of interleukin-10 and interleukin-8, most likely produced by allograft macrophages.