Mechanism of in vitro Antitumor Effects of Interleukin 1 (IL 1)

In vitro studies suggest that purified IL 1 β derived from normal human peripheral blood monocytes and human myelomonocytic cell line THP-1 cell supernatants was capable of modest augmentation of NK activity of purified LGL and of promoting monocyte cytotoxicity for the human melanoma A375 target cells. In addition, purified IL 1 β also has direct cytostatic and cytocidal effects for A375 cells. A375 melanoma cells were cloned to obtain a homogeneous population of IL 1 receptor-bearing target cells. Recombinant human IL 1 α inhibited the proliferation of these cells within 48–72 h in a dose-dependent manner. Similar doses of recombinant IL 1 α exhibited inhibitory effects on the ornithine decarboxylase (ODC) activity of A375 cells by 6–24 h. Putrescine, a nontoxic product of the ODC pathway, could prevent the cytostatic effect of recombinant IL 1 a on these tumor target cells. This observation indicates that inhibition of the ODC pathway is causally related to the antiproliferative effect of IL 1 on these tumor cells.