Systemic release of interleukin-10 during orthotopic liver transplantation.
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 pg/ml (median = 677 pg/ml). 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-gamma, both produced by T cells, and interleukin-8, a cytokine secreted by macrophages, in eight patients. Interleukin-4 and interferon-gamma 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 (< 20 pg/ml) before and after liver allograft reperfusion. Interleukin-10 plasma levels did not correlate either with cold ischemia time or with the occurrence of rejection episodes. We conclude that orthotopic liver transplantation is associated with a massive release of interleukin-10 and interleukin-8, most likely produced by allograft macrophages.
Le Moine
O
O
Department of Gastroenterology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Marchant
A
A
Durand
F
F
Ickx
B
B
Pradier
O
O
Belghiti
J
J
Abramowicz
D
D
Gelin
M
M
Goldman
M
M
Devière
J
J
D000328:Adult; D004731:Endotoxins / Q000097:blood; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008099:Liver / Q000276:immunology / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D013601:T-Lymphocytes / Q000378:metabolism
D004731:Endotoxins; D016209:Interleukin-8; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma