Normal pharmacologically-induced, but decreased regenerative liver growth in interleukin-6-deficient (IL-6−/−) mice

Background/Aims: In the absence of liver damage, rapid liver growth can be induced pharmacologically by so-called primary liver growth promoters. The importance of the acute-phase cytokines interleukin-6 and tumor necrosis factor-α for the actions of these compounds is not clear. This study aimed to investigate the importance of IL-6 and TNF-receptor-1 in pharmacologically-induced liver growth. Methods: IL-6 knockout (IL-6−/−), TNF-receptor-1 knockout (TNFR1−/−) and wild-type mice were treated with the peroxisome proliferator nafenopin and the anti-androgen cyproterone acetate (CPA) in one single injection or for 6 days with daily injections, and examined at 24 or 48 h after treatment. In a control experiment, IL-6−/− mice were subjected to two-thirds partial hepatectomy. Results: Nafenopin treatment increased relative liver weight and DNA synthesis similarly in IL-6−/−, TNFR1−/− and wild-type mice. CPA increased liver weight similarly in all groups, but did not increase DNA synthesis. Expression of peroxisome proliferator activated receptor-α mRNA was increased in both IL-6−/− and wild-type mice by nafenopin treatment, but not by CPA treatment. After hepatectomy DNA synthesis was suppressed in IL-6−/− mice compared to wild-type mice. Conclusions: Liver growth induced by nafenopin and CPA was not dependent on the presence of IL-6 or TNF receptor-1, whereas liver regeneration was decreased in IL-6−/− mice.