Mechanism of in vitro antitumor effects of interleukin 1 (IL 1).
In vitro studies suggest that purified IL 1 beta 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 beta 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 alpha inhibited the proliferation of these cells within 48-72 h in a dose-dependent manner. Similar doses of recombinant IL 1 alpha 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 alpha 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.
D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects; D007375:Interleukin-1 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D008545:Melanoma / Q000473:pathology; D009000:Monocytes / Q000276:immunology; D009955:Ornithine Decarboxylase / Q000378:metabolism; D011700:Putrescine / Q000494:pharmacology
D007375:Interleukin-1; D009955:Ornithine Decarboxylase; D011700:Putrescine