Systemic Release of Interleukin–10 During Orthotopic Liver Transplantation

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Abstract
Experimental and clinical observations indicate that the liver allograft is less immunogenic than other organ transplants and can promote immune tolerance. Because interleukin–10 recently emerged as a macrophage and T–cell–derived cytokine with potent immunosuppressive properties, we studied its production in 28 patients undergoing orthotopic liver transplantation. Plasma levels of immunoreactive interleukin–10 dramatically increased within 2 hr after liver allograft reperfusion, with peak levels ranging between 214 and 4998 pglml (median = 677 pglml). This systemic release of interleukin–10 was transient because it returned to low levels by 48 hr (range = 26 to 51 pg/ml). The higher interleukin–10 levels measured in right atrial blood as compared with portal blood indicated that interleukin–10 was most likely synthesized within the liver graft. To get insight into the cellular origin of interleukin–10, we also measured serum levels of interleukin–4 and interferon–γ, both produced by T cells, and interleukin–8, a cytokine secreted by macrophages, in eight patients. Interleukin–4 and interferon–γ levels remained undetectable in most of the patients, whereas interleukin–8 levels paralleled those of interleukin–10. Portal endotoxemia was probably not involved in interleukin–10 production because endotoxin levels remained low (