Leach M W, Snyder E A, Sinha D P, Rosenblum I Y
Schering-Plough Research Institute, Lafayette, New Jersey 07848, USA.
Clin Immunol Immunopathol. 1997 Apr;83(1):8-11. doi: 10.1006/clin.1997.4303.
Recombinant human IL-4 (rhuIL-4) has been evaluated in a series of preclinical studies. These studies have demonstrated that rhuIL-4 is a very potent cytokine with a wide range of pharmacologic and toxicologic effects. Target systems/organs included the cardiovascular system, liver, spleen, and bone marrow. The incidence and severity of effects correlated strongly with both the dose level and the duration of rhuIL-4 administration. The major dose-limiting toxicities identified included death, cardiac inflammation and necrosis, hepatitis, and hepatic necrosis and occurred at sc doses > or = 25 micrograms/kg/day, while a sc dose of 5 micrograms/kg/day was the highest tested that did not result in major dose-limiting toxicity. Clinical trials in humans have demonstrated that sc administration of Escherichia coli-derived rhuIL-4 is safe and well tolerated at doses up to and including 5 micrograms/kg/day and up to 10 micrograms/kg when administered 3 times/week.
重组人白细胞介素-4（rhuIL-4）已在一系列临床前研究中进行了评估。这些研究表明，rhuIL-4是一种非常有效的细胞因子，具有广泛的药理和毒理作用。靶系统/器官包括心血管系统、肝脏、脾脏和骨髓。效应的发生率和严重程度与rhuIL-4给药的剂量水平和持续时间密切相关。确定的主要剂量限制性毒性包括死亡、心脏炎症和坏死、肝炎以及肝坏死，发生在皮下剂量≥25微克/千克/天，而皮下剂量5微克/千克/天是测试的最高剂量，未导致主要剂量限制性毒性。人体临床试验表明，皮下注射大肠杆菌衍生的rhuIL-4在剂量高达并包括5微克/千克/天以及每周给药3次时剂量高达10微克/千克时是安全的且耐受性良好。
