Role of IL-6 in the induction of hepatic metallothionein in mice after partial hepatectomy

Metallothioneins (MT) are induced upon partial hepatectomy (PH), possibly m ediated by various cytokines. In the present study, we studied cytokine-dep endent MT synthesis in partially hepatectomized IL-6 gene knock-out (GKO) m ice in the remaining lobe of the liver. We focused on IL-6, TNF alpha and I L-1 beta, the major cytokines thought to be involved in MT synthesis. The I L-6 GKO mice and B6J129Sv (wild-type control) mice were subjected to 70% PH or laparotomy. We found that MT was significantly decreased in IL-6 GKO mi ce, although PH induced hepatic MT in both strains of mice. Laparotomy indu ced MT in the liver of wild-type mice but not in IL-6 GKO mice. Pretreatmen t of IL-6 GKO mice with rIL-6 (5 mu g/mouse) restored hepatic MT synthesis. Serum IL-6 level in wild-type mice was maximal at 6 h after surgery and de creased thereafter. Serum IL-1 beta was the same in both strains of mice. S erum TNF alpha basal level in IL-6 GKO mice was higher than in wild-type mi ce. PH caused an increase in serum TNF alpha level in both strains of mice, and it was two times higher in IL-6 GKO mice than in wild-type mice at 18 h after surgery. We conclude that IL-6 plays a predominant role in hepatic MT synthesis after PH, but that IL-6 GKO mice still reserve the capacity to synthesize MT by an as yet unidentified mechanism.