Interleukin 6 Is Important for Survival After Partial Hepatectomy in Mice

The response to partial hepatectomy (PH) is impaired in interleukin 6 (IL–6)–deficient mice. IL–6 is well known for its role in the induction of the acute phase (AP) response, and the impairment of this response after surgery and hepatectomy could explain the defective hepatocyte regeneration. In addition, it was proposed that IL–6 has an important role in stimulating the reentry of quiescent cells into the cell cycle within the first 2 to 4 hours after PH. To further analyze the role for IL–6, we performed two third hepatectomies in wild–type mice, in IL–6 knockout (KO) mice, and in IL–6 KO mice that were treated 30 minutes before surgery with intravenous (IV) (short acting) or subcutaneous (SC) (long acting) injections of recombinant IL–6. The high postoperative mortality of IL–6–deficient mice could be completely prevented by SC, but not by IV IL–6 treatment, showing the requirement of a sustained action of IL–6. However, there is a subset of IL–6 KO mice that survives a PH in good health even without IL–6 treatment. When we analyzed these mice, we found an intact liver regeneration and no indication of a block in cell cycle reentry. We conclude that the major role of IL–6 is the induction of an adaptive response to PH that ensures body homeostasis and survival.