Cytokine gene expression in liver following minor or major hepatectomy in rat

Interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), and transforming growth factors alpha and beta (TGF-alpha and TGF-beta) are important mediators which play a pleiotropic role 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 influence of minor (30%) vs major (80%) hepatectomy on cytokines, growth factors and acute-phase proteins both at the protein and mRNA levels in rat, For that purpose, rats were submitted to either 30% or 80% hepatectomy and sacrified at intervals up to day 14 post-hepatectomy to collect liver and blood samples, Serum levels of IL-6 and acute-phase proteins (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 were early upregulated after a 80% resection only, whereas liver mRNA levels for IL-1 slowly increased following 30 or 80% hepatectomy, For TNF-alpha, no significant changes were observed between groups, Growth factor expression differed according to the extent of hepatic resection. Moreover, plasma levels of alpha(2)-macroglobulin (alpha 2M) and alpha 1 acid glycoprotein (ACP), two major APPs which respond differently to combination of cytokines, were significantly lowered after a major resection whereas levels of serum IL-6 showed no significant changes between groups, Paradoxically,, in the 80% hepatectomized group, alpha 2M mRNA expression was strongly increased at 4 h and 6 h post-hepatectomy as compared with the 30% hepatectomized group, Taken together, these results suggest that, although an increased level of hepatic IL-6 expression was observed following a major resection, the liver's capacity to synthesize normal levels of APPs was impaired, Moreover, these specific changes of cytokine gene expression seen in the liver following major hepatectomy might reflect a preferential activation of the IL-6-dependent APPs. (C) 1997 Academic Press Limited.