Regulation of liver regeneration by interleukin-2 and its inhibitors: cyclosporine A and FK 506.

Several investigations have been suggesting that lymphocytes can be responsible for growth regulation of liver. The interleukin-2 (IL-2) production by spleen cells was noted to be increased 2 days after resection of 70% of the volume of the liver in C3H/He mice. The effects of IL-2 production and its antagonists: cyclosporine A (CsA) and FK506 on liver regeneration were thus studied by measuring in vivo incorporation of Bromodeoxyuridine (BrdU). By intraperitoneal injection of IL-2 5 times every 8 h after hepatectomy. BrdU labeling indices at 36 h after the operation were suppressed in a dose-dependent manner. On the other hand, treatment with CsA and FK506, which inhibit IL-2 production, increased the mitotic indices of the regenerating livers. Serum levels of aminotransferases were not affected by FK506 at a dose sufficient for the mitotic stimulation. Based on these results, CsA and FK506 would appear to stimulate liver cell proliferation by suppressing IL-2 production and inhibiting of NK cell activity.