Farace F, Mathiot C, Brandely M, Tursz T, Dorval T, Pouillart P, Triebel F, Hercend T, Fridman W H
Institut Gustave Roussy, Villejuif, France.
Clin Exp Immunol. 1990 Nov;82(2):194-9. doi: 10.1111/j.1365-2249.1990.tb05426.x.
Alterations of immunological parameters were analysed in patients with advanced malignancies during a phase I trial with rIL-2. Five-day infusions of rIL-2 at doses from 1 x 10(6) to 24 x 10(6) biological response modifiers program (BRMP) U/m2 per day were given to 29 patients, with a minimum of three patients per dose. The dose of 24 x 10(6) U/m2 per day was the maximal tolerated dose (MTD). Immunological parameters were analyzed at days 0, 8 and 11 of the rIL-2 courses. Following a leucopenia during rIL-2 infusion, a lymphocytosis was found in all patients except one. The lymphocytosis peaked at day 8 and was detected at doses of rIL-2 as low as 1 x 10(6) U/m2 per day, reaching a plateau at a dose of 16 x 10(6) U/m2 per day. Although all lymphocyte subsets were increased in patients receiving rIL-2, some patients had predominant T cells (CD3+, NKH1(CD56)-), others had predominant natural killer (NK) cells (CD3-, NKH1 (CD56)+), and yet others showed a mixed profile. A strong induction of cells cytotoxic for K562 targets was found in all patients at days 8 and 11. Eighteen patients received, 1 month later, a second treatment in which infusion of rIL-2 was preceded by a course of 5 days infusion of 2 x 10(6) U/m2 per day recombinant interferon-gamma (rIFN-gamma). The infusion of rIFN-gamma prior to rIL-2 had no effect on the rIL-2-induced alterations of immunological parameters. Taken together, our results suggest that immune stimulation by rIL-2 occurs even at low doses and is maximal at a dose below the MTD; and that pretreatment with low-dose rIFN-gamma does not modify the immune stimulation by rIL-2.
在一项使用重组白细胞介素-2（rIL-2）的I期试验中，对晚期恶性肿瘤患者的免疫参数改变进行了分析。29例患者接受了为期5天的rIL-2输注，剂量为每天1×10⁶至24×10⁶生物反应调节剂程序（BRMP）单位/平方米，每个剂量组至少有3例患者。每天24×10⁶单位/平方米的剂量是最大耐受剂量（MTD）。在rIL-2疗程的第0、8和11天分析免疫参数。在rIL-2输注期间出现白细胞减少后，除1例患者外，所有患者均出现淋巴细胞增多。淋巴细胞增多在第8天达到峰值，在低至每天1×10⁶单位/平方米的rIL-2剂量时即可检测到，在每天16×10⁶单位/平方米的剂量时达到平台期。虽然接受rIL-2的患者所有淋巴细胞亚群均增加，但一些患者以T细胞（CD3⁺、NKH1(CD56)⁻）为主，另一些患者以自然杀伤（NK）细胞（CD3⁻、NKH1(CD56)⁺）为主，还有一些患者表现为混合特征。在第8天和第11天，所有患者均发现对K562靶细胞具有细胞毒性的细胞被强烈诱导。18例患者在1个月后接受了第二次治疗，在输注rIL-2之前，先进行了为期5天、每天2×10⁶单位/平方米的重组干扰素-γ（rIFN-γ）输注疗程。在rIL-2之前输注rIFN-γ对rIL-2诱导的免疫参数改变没有影响。综上所述，我们的结果表明，rIL-2即使在低剂量时也能产生免疫刺激，且在低于MTD的剂量时刺激最大；低剂量rIFN-γ预处理不会改变rIL-2的免疫刺激作用。
