van Gameren M M, Willemse P H, Mulder N H, Limburg P C, Groen H J, Vellenga E, de Vries E G
Department of Internal Medicine, University Hospital, Groningen, The Netherlands.
Blood. 1994 Sep 1;84(5):1434-41.
To define the toxicity profile of recombinant human interleukin-6 (rhIL-6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6-related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL-6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.
为明确重组人白细胞介素-6（rhIL-6）的毒性特征，并研究其对造血、生化参数及其他细胞因子的影响，在一项I-II期研究中，对20例乳腺癌或非小细胞肺癌患者给予rhIL-6。rhIL-6的剂量分别为0.5、1.0、2.5、5.0、10和20微克/千克/天，每个剂量水平至少有3例患者。rhIL-6通过持续静脉输注给药24小时，随后皮下（SC）给药6天，部分为门诊给药。与rhIL-6相关的副作用包括发热、头痛、肌痛和局部红斑。从2.5微克/千克/天开始，这些副作用还伴有恶心、肝酶可逆性升高和贫血。使用对乙酰氨基酚，类流感症状在rhIL-6剂量达10微克/千克/天及以下时均可控制。rhIL-6可使血小板计数增加，平均血小板体积减小，还可使白细胞增加，这是由中性粒细胞、单核细胞和淋巴细胞增多所致，在rhIL-6剂量为1.0和2.5微克/千克/天时，T细胞和自然杀伤细胞也增加。可逆性贫血的特征为血清铁降低，铁蛋白和促红细胞生成素升高，且无网织红细胞增多。rhIL-6可降低总胆固醇水平，且观察到C反应蛋白和血清淀粉样蛋白A血浆水平呈剂量相关增加。血清IL-6水平升高，尤其是在剂量为10和20微克/千克/天时，而IL-1β和肿瘤坏死因子α水平未观察到变化。在此情况下，rhIL-6给药的副作用可控，门诊给药时SC剂量达10微克/千克/天及以下，且对白细胞生成和血小板生成具有良好的刺激作用。
