CYTOKINE GENE-EXPRESSION IN LIVER FOLLOWING MINOR OR MAJOR HEPATECTOMY IN RAT

Interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), interl eukin 1 (IL-1), and transforming growth factors alpha and beta (TGF-al pha and TGF-beta) are important mediators which play a pleiotropic rol e in both inflammatory and hepatic regeneration processes, It has also been proposed that a major hepatectomy impairs the liver-related host defence mechanisms, The aim of this study was to evaluate the influen ce of minor (30%) vs major (80%) hepatectomy on cytokines, growth fact ors and acute-phase proteins both at the protein and mRNA levels in ra t, For that purpose, rats were submitted to either 30% or 80% hepatect omy and sacrified at intervals up to day 14 post-hepatectomy to collec t liver and blood samples, Serum levels of IL-6 and acute-phase protei ns (APPs) were determined and after RNA extraction, cytokine and acute -phase proteins gene expression were evaluated using a quantitative RT -PCR method, The results demonstrate that liver mRNA levels for IL-6 w ere early upregulated after a 80% resection only, whereas liver mRNA l evels for IL-1 slowly increased following 30 or 80% hepatectomy, For T NF-alpha, no significant changes were observed between groups, Growth factor expression differed according to the extent of hepatic resectio n. Moreover, plasma levels of alpha(2)-macroglobulin (alpha 2M) and al pha 1 acid glycoprotein (ACP), two major APPs which respond differentl y to combination of cytokines, were significantly lowered after a majo r resection whereas levels of serum IL-6 showed no significant changes between groups, Paradoxically,, in the 80% hepatectomized group, alph a 2M mRNA expression was strongly increased at 4 h and 6 h post-hepate ctomy as compared with the 30% hepatectomized group, Taken together, t hese results suggest that, although an increased level of hepatic IL-6 expression was observed following a major resection, the liver's capa city to synthesize normal levels of APPs was impaired, Moreover, these specific changes of cytokine gene expression seen in the liver follow ing major hepatectomy might reflect a preferential activation of the I L-6-dependent APPs. (C) 1997 Academic Press Limited.