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Abstracts - Chirurgie Kongress

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Research – Infection / Immunity 23<br />

23.1<br />

Interleukin-1 receptor antagonist improves liver regeneration<br />

A. Sgroi, C. Gonelle-Gispert, P. Morel, R. Baertschiger, V. Serre-Beinier, L. Buhler (Genève)<br />

Objective: Living donor liver transplantation may be complicated by small for size syndrome and improvement<br />

of liver regeneration by cytokine therapy is a potential solution to this problem. The aim of<br />

this study was to evaluate the role of interleukin-1 receptor antagonist (IL-1ra) in liver regeneration after<br />

partial hepatectomy and to study the effect of anakinra, a non glycosylated recombinant human IL-1ra,<br />

on liver regeneration.<br />

Methods: We performed 70%-hepatectomy in wild type (WT) mice, IL-1ra knock-out (KO) mice and in<br />

WT mice treated by anakinra (50mg/kg/d i.p.). After hepatectomy, we analyzed at regular intervals:<br />

(i) blood levels of cytokines and growth factors implicated in liver regeneration (i.e. TNF-α, IL-6, HGF,<br />

TGF-α1, IL-1α, IL-1ra, MCP-1 and IL12p70) by enzyme-linked immunosorbent assay or by fluorescenceactivated<br />

cell sorting; (ii) proliferation of native hepatocytes following bromodeoxydurine incorporation<br />

(BrdU) measured by immunohistochemistry and proliferating cell nuclear antigen (PCNA) and Cyclin<br />

D1 expression by western blot analysis on native liver tissue.<br />

Results: IL-1ra KO mice showed a significant increase of serum levels of pro-inflammatory cytokines<br />

implicated in liver regeneration compared to wild type mice (IL-6, MCP-1 and TNF-α at 4h post-hepatectomy).<br />

IL-1ra KO mice had a significant lower hepatocyte proliferation after hepatectomy at 24h and<br />

48h compared to wild type mice (BrdU incorporation 4% versus 1% at 24h; 32% versus 14% at 48h,<br />

13% versus 14% at 72h, respectively, p

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