Crump W L, Owen-Schaub L B, Grimm E A
Department of Tumor Biology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Cancer Res. 1989 Jan 1;49(1):149-53.
Peripheral blood mononuclear cells cultured in vitro with interleukin 2 (IL-2) become cytolytic towards both autologous and allogeneic tumor cells. We report here that IL-1 synergizes with IL-2 in serum-free conditions to produce increased (1.3-286-fold) lymphokine-activated killer (LAK) activity. The most dramatic synergy is seen with low IL-2 concentrations (10 U/ml, 222 pM) and 50-250 U/ml IL-1 alpha or beta. Kinetics of addition experiments demonstrate a specific requirement for IL-1 at or before addition of IL-2 to the culture. We postulate that one of the mechanisms whereby IL-1 augments LAK activity is by rendering LAK-precursors more responsive to IL-2. Up-regulation of the IL-2 receptor beta chain (Tac) and increased [3H]thymidine incorporation in cultures containing IL-1 and IL-2 support this view. In some instances, IL-1 alone is capable of maintaining/generating a small degree of cytolytic activity. Collectively, our data demonstrate that IL-1 is capable of interacting with low dose IL-2 to significantly augment LAK activity, potentially playing an important role in the early stages of LAK activation and differentiation. Because synergy is observed with dramatically reduced IL-2 concentrations, this system may offer an alternative approach to high dose IL-2 therapy for the treatment of neoplastic disease.
在体外与白细胞介素2（IL-2）一起培养的外周血单核细胞对自体和异体肿瘤细胞均具有细胞溶解作用。我们在此报告，在无血清条件下，IL-1与IL-2协同作用可产生增强的（1.3至286倍）淋巴因子激活的杀伤细胞（LAK）活性。在低IL-2浓度（10 U/ml，222 pM）和50至250 U/ml的IL-1α或β存在时，可观察到最显著的协同作用。添加实验的动力学表明，在向培养物中添加IL-2时或之前，对IL-1有特定需求。我们推测，IL-1增强LAK活性的机制之一是使LAK前体细胞对IL-2更敏感。在含有IL-1和IL-2的培养物中，IL-2受体β链（Tac）的上调以及[3H]胸苷掺入增加支持了这一观点。在某些情况下，单独的IL-1能够维持/产生一定程度的细胞溶解活性。总体而言，我们的数据表明，IL-1能够与低剂量IL-2相互作用，显著增强LAK活性，可能在LAK激活和分化的早期阶段发挥重要作用。由于在显著降低的IL-2浓度下观察到协同作用，该系统可能为肿瘤疾病的高剂量IL-2治疗提供一种替代方法。
