Onozaki K, Matsushima K, Aggarwal B B, Oppenheim J J
J Immunol. 1985 Dec;135(6):3962-8.
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.
从受刺激的人单核细胞中获得的高度纯化的白细胞介素1（IL-1）似乎对人黑色素瘤细胞系A375具有生长抑制和细胞杀伤作用。虽然IL-1没有立即的细胞溶解作用，但随着培养时间的延长，靶细胞的生长受到不可逆的抑制。细胞最终裂解，数量显著减少；因此可以说IL-1的作用是细胞杀伤性的。通过使用常规和高效液相色谱（HPLC）的各种色谱方法，IL-1活性不能与细胞杀伤活性分离。A375黑色素瘤细胞系对源自人B细胞系的另一种人细胞因子α-淋巴毒素（α-LT）也敏感。IL-1对LT敏感的小鼠成纤维细胞系L929似乎也有部分生长抑制和细胞杀伤作用；但对LT抗性细胞没有作用，包括L929的一个亚系；人上皮癌细胞系HeLa；人骨肉瘤细胞系HOS；以及小鼠SV40转化的肾细胞系TU5。然而，LT敏感的小鼠成纤维细胞系L-M对IL-1有抗性。因此，IL-1的细胞杀伤活性仅部分重叠α-LT的靶细胞选择性。虽然天然IFN-α和重组IFN-β对A375细胞系有明显的生长抑制作用，但天然和重组IFN-α、重组IFN-β和IFN-γ几乎没有细胞杀伤活性。纯化的IL-1没有任何抗病毒活性，相反，IFN和α-LT对胸腺细胞没有协同促有丝分裂作用。此外，通过ELISA和放射免疫测定，抗人α-LT、肿瘤坏死因子和IFN-γ的抗体不与IL-1反应，表明IL-1在抗原性上与这些其他细胞因子不同。这些体外结果表明，IL-1作为一种细胞杀伤因子可能在宿主抵抗某些肿瘤的防御中发挥作用。
