Sechler J M, Malech H L, White C J, Gallin J I
Bacterial Diseases Section, National Institute of Allergy and Infectious Diseases, Bethesda, MD 20892.
Proc Natl Acad Sci U S A. 1988 Jul;85(13):4874-8. doi: 10.1073/pnas.85.13.4874.
Monocytes from 19 of 30 patients with the classic phenotype of chronic granulomatous disease of childhood (CGD) responded to 3 days of treatment in culture with recombinant human interferon-gamma (rHuIFN-gamma) at 100 units/ml by producing superoxide after stimulation with phorbol 12-myristate 13-acetate. Cells from 15 of 16 patients with cytochrome b-positive CGD (15 with autosomal and 1 with X chromosome-linked inheritance) and cells from 4 of 14 patients with cytochrome b-negative CGD (13 with X chromosome-linked and 1 with autosomal recessive inheritance) responded. Subcutaneous rHuIFN-gamma (0.01-0.05 mg/m2) administered as a single dose, daily or every other day, for five or six doses to 3 patients whose phagocytes responded to rHuIFN-gamma in vitro resulted in significant improvement in phagocyte bactericidal activity against Staphylococcus aureus and increases in superoxide production. Studies on 1 patient's cells indicated the increases in superoxide production correlated with increased membrane cytochrome b. The effects of rHuIFN-gamma persisted for more than a week following cessation of therapy. Thus, we have demonstrated a partial correction in vivo of these CGD patients' phagocyte defect with rHuIFN-gamma. Moreover, the data suggest that a significant proportion of patients with CGD will respond to rHuIFN-gamma with augmentation of phagocyte microbicidal function.
30例具有典型儿童慢性肉芽肿病（CGD）表型的患者中，19例患者的单核细胞在体外培养时，用100单位/毫升的重组人干扰素-γ（rHuIFN-γ）处理3天，经佛波酯12-肉豆蔻酸酯13-乙酸酯刺激后能产生超氧化物。16例细胞色素b阳性CGD患者（15例常染色体遗传和1例X染色体连锁遗传）中的15例患者的细胞，以及14例细胞色素b阴性CGD患者（13例X染色体连锁遗传和1例常染色体隐性遗传）中的4例患者的细胞有反应。对3例体外吞噬细胞对rHuIFN-γ有反应的患者，皮下注射单剂量、每日或隔日一次的rHuIFN-γ（0.01 - 0.05毫克/平方米），共注射五或六剂，结果显示对金黄色葡萄球菌的吞噬细胞杀菌活性显著改善，超氧化物产生增加。对1例患者细胞的研究表明，超氧化物产生的增加与膜细胞色素b的增加相关。治疗停止后，rHuIFN-γ的作用持续超过一周。因此，我们已证明rHuIFN-γ可在体内部分纠正这些CGD患者的吞噬细胞缺陷。此外，数据表明，相当一部分CGD患者对rHuIFN-γ有反应，其吞噬细胞杀菌功能增强。
