Vey N, Viens P, Fossat C, Olive D, Sainty D, Baume D, Stoppa A M, Bouabdallah R, Brandely M, Gastaut J A, Maraninchi D, Blaise D
Institut Paoli-Calmettes and INSERM Unit 119, Marseille, France.
Eur Cytokine Netw. 1997 Dec;8(4):389-94.
Interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) have shown synergistic immunomodulatory and anti-tumor effects in preclinical studies. The present study was designed to assess the effects of the combination of these cytokines after autologous bone marrow transplantation (ABMT). Ten patients received rIFN-gamma alone and 13 patients the combination of rIFN-gamma + rIL-2. Patients received transplants because of lymphoma (10 patients), acute leukemia (3 patients) or solid tumors (10 patients). Immunotherapy was started at a median of 67 days after ABMT. All patients received either 5 x 10(6) (8 pts) or 10 x 10(6) IU/m2 (16 pts) rIFN-gamma by subcutaneous injection 3 times weekly for 14 weeks. rIL-2 therapy consisted of 5 cycles of continuous intravenous infusion of 12 x 10(6) IU/m2/day starting 1 week after administration of rIFN-gamma. In the rIFN-gamma group, toxicity was mild and some biological changes were seen (NK/LAK activation, increase of phagocytosis and of NBT reduction). The combination of rIFN-gamma with rIL-2 did not increase the usual rIL-2 toxicity. NK/LAK cytotoxicity was strongly activated after the first cycle of rIL-2 and was maintained until the end of therapy. Granulocyte chemotaxis was defective after cycle 1 but recovered thereafter. We conclude that the administration of rIFN-gamma + rIL-2 is feasible after ABMT. Our data suggest that the combination may have prolonged the immunologic activation provided by rIL-2 and some improvement of the deleterious effects of rIL-2 on granulocyte functions was achieved. Controlled studies are warranted to assess the impact of this strategy on biological response and patient outcome.
γ干扰素（IFN-γ）和白细胞介素-2（IL-2）在临床前研究中已显示出协同的免疫调节和抗肿瘤作用。本研究旨在评估自体骨髓移植（ABMT）后这两种细胞因子联合应用的效果。10例患者单独接受重组IFN-γ，13例患者接受重组IFN-γ + 重组IL-2联合治疗。患者因淋巴瘤（10例）、急性白血病（3例）或实体瘤（10例）接受移植。免疫治疗在ABMT后中位67天开始。所有患者每周皮下注射3次5×10⁶（8例）或10×10⁶ IU/m²（16例）重组IFN-γ，共14周。重组IL-2治疗包括在给予重组IFN-γ后1周开始连续5个周期静脉输注12×10⁶ IU/m²/天。在重组IFN-γ组，毒性轻微，可见一些生物学变化（NK/LAK激活、吞噬作用增加和NBT还原增加）。重组IFN-γ与重组IL-2联合应用未增加重组IL-2的常见毒性。重组IL-2第一个周期后NK/LAK细胞毒性强烈激活，并维持至治疗结束。第1周期后粒细胞趋化性有缺陷，但此后恢复。我们得出结论，ABMT后给予重组IFN-γ + 重组IL-2是可行的。我们的数据表明，联合应用可能延长了重组IL-2提供的免疫激活时间，并在一定程度上改善了重组IL-2对粒细胞功能的有害影响。有必要进行对照研究以评估该策略对生物学反应和患者预后的影响。
