Abstracts - Chirurgie Kongress
Abstracts - Chirurgie Kongress
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