PARTIAL CORRECTION OF THE PHAGOCYTE DEFECT IN PATIENTS WITH X-LINKED CHRONIC GRANULOMATOUS-DISEASE BY SUBCUTANEOUS INTERFERON-GAMMA
PARTIAL CORRECTION OF THE PHAGOCYTE DEFECT IN PATIENTS WITH X-LINKED CHRONIC GRANULOMATOUS-DISEASE BY SUBCUTANEOUS INTERFERON-GAMMA
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DOI：
10.1056/nejm198807213190305
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发表时间：
1988-07-21
影响因子：
158.5
通讯作者：
NEWBURGER, PE
中科院分区：
文献类型：
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作者：
EZEKOWITZ, RAB;DINAUER, MC;NEWBURGER, PE
慢性肉芽肿病是一种宿主防御障碍，其特征是由于吞噬细胞产生超氧阴离子的缺陷而导致杀死微生物的能力受损。我们检查了干扰素γ的疗效，一种吞噬细胞功能的生理激活剂，在治疗疾病。四名x连锁型患者连续几天接受两次重组干扰素γ皮下注射（每剂量体表面积0.1毫克）。治疗导致粒细胞和单核细胞产生的超氧化物增加5- 10倍；这种改善持续了两个多星期。粒细胞杀菌活性呈比例上升。在两名反应最积极的患者中，两种吞噬功能均达到正常活动范围。与这些功能变化相关的是，我们观察到吞噬细胞细胞色素b（产生超氧化物氧化酶的关键成分）和免疫反应性细胞色素b重链（x连锁慢性肉芽肿病中缺陷基因的产物）的细胞含量增加。通过分光光度法检测到的细胞色素b水平从接近零上升到正常值的10%到50%。本研究证实干扰素γ可部分纠正慢性肉芽肿病的细胞缺陷，为该药物的临床试验提供依据。
Chronic granulomatous disease, a disorder of host defense, is characterized by an impairment in the killing of microbes that results from a defect in the production of superoxide anion by phagocytes. We examined the efficacy of interferon gamma, a physiologic activator of phagocytic-cell function, in the treatment of the disease. Two subcutaneous injections of recombinant interferon gamma (0.1 mg per square meter of body-surface area per dose) were administered on consecutive days to four patients with the X-linked form of the disease. Treatment resulted in 5- to 10-fold increases in superoxide production by granulocytes and monocytes; the improvement was sustained for more than two weeks. Granulocyte bactericidal activity rose proportionally. In the two most responsive patients, both phagocytic functions reached the normal range of activity. In association with these functional changes, we observed an increase in cellular contents of phagocyte cytochrome b (a critical component of the superoxide-producing oxidase) and immunoreactive cytochrome b heavy chain (the product of the gene that is defective in X-linked chronic granulomatous disease). Levels of cytochrome b detected by spectrophotometry rose from near zero to 10 to 50 percent of normal values. This study demonstrates partial correction of the cellular defects in chronic granulomatous disease by interferon gamma and provides a basis for clinical trials of the agent.