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Using the primary culture of liver cells, we showed that interferon produced by nonparenchymal liver cells inhibits the proliferation of cultured parenchymal liver cells. DNA synthesis of parenchymal liver cells was suppressed not only by their coculture with nonparenchymal liver cells but also by the addition of the culture supernatant of nonparenchymal liver cells. The suppressive activity of the supernatant correlated closely with the interferon (alpha + beta) level in the supernatant and was reduced by anti interferon (alpha + beta) serum. Furthermore, purified interferon (alpha + beta) also suppressed parenchymal liver cell proliferation in a dose-dependent manner and the suppression was released by anti interferon (alpha + beta) serum. The interferon level of the supernatant necessary for suppressing parenchymal liver cell proliferation, however, was extraordinarily low compared with purified interferon. The possibility exists that IFN in the culture supernatant of nonparenchymal liver cells works synergistically with other factors in the supernatant to suppress the cell proliferation.

Growth control of primary culture hepatocytes by nonparenchymal liver cells. Role of interferon produced by liver sinusoidal cells.