Human interleukin 1 is a cytocidal factor for several tumor cell lines.
Highly purified interleukin 1 (IL 1) obtained from stimulated human monocytes appeared to be growth inhibitory and cytocidal for a human melanoma cell line, A375. Although IL 1 did not have an immediate cytolytic effect, with time in culture the growth of the target cells was irreversibly inhibited. The cells eventually lysed and decreased markedly in number; the IL 1 effect can therefore be said to be cytocidal. IL 1 activity could not be separated from the cytocidal activity by a variety of chromatography procedures by using conventional and high-performance liquid chromatography (HPLC). The A375 melanoma cell line was also sensitive to another human cytokine alpha-lymphotoxin (alpha-LT) derived from a human B cell line. IL 1 also appeared to be partially growth inhibitory and cytocidal for a LT-sensitive mouse fibroblast cell line, L929; but not for LT-resistant cells, including a subline of L929; a human epithelial carcinoma cell line, HeLa; a human osteosarcoma cell line, HOS; and a mouse SV40-transformed kidney cell line, TU5. However, the LT-sensitive mouse fibroblast cell line, L-M, was resistant to IL 1. Therefore, the cytocidal activity of IL 1 only partially overlapped the target cell selectivity of alpha-LT. Although natural IFN-alpha and recombinant IFN-beta were appreciably growth inhibitory for the A375 cell line, natural and recombinant IFN-alpha and recombinant IFN-beta and IFN-gamma exhibited little cytocidal activity. Purified IL 1 did not have any antiviral activity, and conversely, IFN and alpha-LT were not co-mitogenic for thymocytes. Furthermore, by ELISA and radioimmunoassays, antibodies against human alpha-LT, tumor necrosis factor, and IFN-gamma did not react with IL 1, indicating that IL 1 is antigenically distinct from these other cytokines. These in vitro results suggest that IL 1 may play a role in host defense against some tumors as a cytocidal factor.
K
K
Onozaki
K
K
Matsushima
B B
BB
Aggarwal
J J
JJ
Oppenheim
D000818:Animals; D000970:Antineoplastic Agents / Q000502:physiology*; D002460:Cell Line; D003114:Colony-Forming Units Assay; D006131:Growth Inhibitors / Q000502:physiology*; D006367:HeLa Cells / Q000473:pathology; D006801:Humans; D007372:Interferons / Q000494:pharmacology; D007375:Interleukin-1 / Q000502:physiology*; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008545:Melanoma / Q000473:pathology; D051379:Mice; D012516:Osteosarcoma / Q000473:pathology
D000970:Antineoplastic Agents; D006131:Growth Inhibitors; D007375:Interleukin-1; D008233:Lymphotoxin-alpha; D007372:Interferons