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《ISPN学习》总第592期
日期：2020-03-09 21:31:37
《ISPN学习》2020年02月12日总第592期
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★ ISPN Review ★
Interleukins 白细胞介素类
Interleukins are synthetic compounds much like the interleukins; they communicate between lymphocytes, which stimulate cellular immunity and inhibit tumor growth. Interleukin-2 stimulates cellular immunity by increasing the activity of natural killer cells, platelets, and cytokines. Two interleukin preparations are available for use. Aldesleukin (Proleukin) is a human interleukin produced by recombinant DNA technology using E. coli bacteria. Oprelvekin (Neumega) is a newer agent that is also produced by DNA technology.
白细胞介素为合成化合物。在淋巴细胞间起沟通作用，刺激细胞免疫力，抑制肿瘤生长。白细胞介素2增强天然杀伤细胞、血小板和细胞因子类活性，刺激细胞免疫力。目前可用的白细胞介素制剂有2种：阿地白介素（普留净）是一种人白介素，利用大肠杆菌细菌通过基因重组技术生产；奥普瑞白介素（纽密伽）是一种新药，也是通过DNA技术生产的。
Therapeutic Actions and Indications 治疗作用和适应症
Natural interleukin-2 is produced by various lymphocytes to activate cellular immunity and inhibit tumor growth by increasing lymphocyte numbers and their activity. When interleukins are administered, there are increases in the numbers of natural killer cells and lymphocytes, in cytokine activity, and in the number of circulating platelets.
天然白介素2来源于淋巴细胞，通过增加淋巴细胞数量增强淋巴细胞活性，活化细胞免疫力，抑制肿瘤生长。使用白介素后，自然杀伤细胞数量增加，细胞因子活性增强，循环血小板数量增加。
Pharmacokinetics 药代动力学
The interleukins are rapidly distributed after injection. Aldesleukin, given IV, reaches peak levels in 13 minutes and has a half-life of 85 minutes. Oprelvekin, which is given subcutaneously, reaches peak levels in 3 to 5 hours and had a half-life of 7 to 8 hours. They are primarily cleared from the body by the kidneys.
注射后，白介素快速分布。阿地白介素，IV，13分钟达峰，半衰期85分钟；奥普瑞白介素，SQ，3-5小时达峰，半衰期7-8小时。主要经肾清除。
Contraindications and Cautions 禁忌症和注意事项
Interleukins are contraindicated in the presence of any allergy to an interleukin or E. coli–produced product. They were shown to be embryocidal and teratogenic in animal studies and should not be used during pregnancy. Use of barrier contraceptives is recommended for women of childbearing age who require one of these drugs. It is not clear whether the drugs cross into breast milk, but it is recommended that they not be used during lactation; if they must be used, another method of feeding the baby must be chosen because of the potential for adverse effects in the baby. Caution should be used with renal, liver, or cardiovascular impairment because of the adverse effects of the drugs.
对白介素或大肠杆菌产品过敏者禁忌使用白细胞介素。动物研究表明，白介素类有杀胚胎和致畸性，妊娠时不应使用。建议需要其中一种药物的育龄期妇女使用屏障避孕措施。药物是否进入母乳尚不清楚，建议哺乳期不要使用这些药物；如果必须使用，最好采用别的婴儿喂养方式，因为这些药物对婴儿具有潜在的不良效应。肾、肝或心血管受损者慎用，这也是由于药物的不良效应。
Adverse Effects 不良效应
The adverse effects associated with the interleukins can be attributed to their effect on the body during inflammation (flu-like effects: lethargy, myalgia, arthralgia, fatigue, fever). Respiratory difficulties, CNS changes, and cardiac arrhythmias also have been reported, and the patient should be monitored for these effects and the drug stopped if they do occur. Oprelvekin has been associated with severe hypersensitivity reactions, and patients should be closely watched when beginning therapy and encouraged to report any difficulty breathing or swallowing, chest tightness, or swelling.
与白介素相关的不良效应可归因于炎症期间这些药物对身体的效应（出现流感样效应：倦怠、肌痛、关节痛、疲劳、发烧）。呼吸困难、CNS变化、心脏节律异常也有报告；因此，患者应监测有无这些效应，一旦出现就要停药。奥普瑞白介素与严重的过敏性反应相关，开始治疗时，患者应密切监督，出现呼吸困难或吞咽困难、胸闷或浮肿时应立即报告。
★ Vocabulary for Today ★
interleukin – n. 白细胞介素类
natural killer cells – 天然杀伤细胞
cytokine – n. 细胞因子
aldesleukin – n. 阿地白介素
Proleukin – n. 普留净
oprelvekin – n. 奥普瑞白介素
Neumega – n. 纽密伽
embryocidal – a. 杀胚胎的
attribute to – 把…归因于
arthralgia – n. 关节痛
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★ Video ★
Cytokines
★ Test ★
1. A 67-year-old man injures his shoulder in an ATV accident. Over-the-counter ibuprofen is unable to control the pain satisfactorily. The patient asks about glucocorticoid injections, so his doctor begins to explain the myriad effects of glucocorticoids in the body. Which of the following glucocorticoid actions would be most desirable in this patient?
A. Antiemetic
B. Decreasing synthesis of HGF, a growth factor
C. Decreasing translocation of GLUT4 receptors to the cell membrane
D. Increasing synthesis of IkB
2. A 21-year-old woman complains of heavy menstrual bleeding and cramping. She is taking a large class load at a local university and says her periods are interfering with her academic performance. Her physician prescribes a drug that interferes with E2 synthesis in the ovary. Which drug is this?
A. Danazol
B. Estradiol valerate
C. Misoprostol
D. Naproxen
答案
Key to Questions
1. D: Increasing synthesis of IkB.
Glucocorticoids affect many cell types in the body. In this case, the patient would benefit most from inhibiting inflammation. All the responses listed are known glucocorticoid effects, but only increasing synthesis of IkB would decrease inflammation. IkB inhibits NF-kB, which is a transcription factor for enzymes that make inflammatory cytokines.
2. A: Danazol.
Heavy menstrual bleeding, or menorrhagia, can have many causes. Often, neoplasm must be ruled out. One way to decrease pain and excessive bleeding during menstruation is to decrease the amount of circulating estradiol (E2). Danazol causes a decrease in the ovarian production of E2 precursors to decrease E2 production.
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