Shah P L, Scott S F, Knight R A, Hodson M E
Dept of Cystic Fibrosis, Royal Brompton Hospital, London, UK.
Eur Respir J. 1996 Mar;9(3):531-4. doi: 10.1183/09031936.96.09030531.
In cystic fibrosis (CF), neutrophil-dominated airway inflammation results in high levels of neutrophil elastase (NE). Some of these proteases are sequestered by the large amounts of deoxyribonucleic acid (DNA) present in purulent sputum. Recombinant human deoxyribonuclease (rhDNase), a new treatment in CF, depolymerizes DNA. Our concerns were that this might release proteases bound to DNA, which could be potentially harmful. The in vitro and in vivo effects of rhDNase on NE and interleukin-8 (IL-8) were evaluated. The acute effects of rhDNase were evaluated in CF patients during the first 6 days of treatment. Medium-term effects were evaluated in stable CF patients observed in rhDNase over 6 months. Sputum samples were collected at regular intervals and NE activity was measured by a fluorimetric assay and IL-8 with a radioimmunoassay. In vitro addition of rhDNase resulted in a twofold increase in protease activity and this was reflected in an acute transient rise on initiation of treatment with rhDNase. Medium-term treatment was associated with a decline in NE activity and IL-8. These in vivo results are encouraging, since the increase in protease activity was transient and the trend over 6 months was a reduction in both inflammatory markers.
在囊性纤维化（CF）中，以中性粒细胞为主的气道炎症会导致高水平的中性粒细胞弹性蛋白酶（NE）。这些蛋白酶中的一些会被脓性痰液中大量存在的脱氧核糖核酸（DNA）所隔离。重组人脱氧核糖核酸酶（rhDNase）是CF的一种新疗法，可使DNA解聚。我们担心这可能会释放与DNA结合的蛋白酶，而这些蛋白酶可能具有潜在危害。评估了rhDNase对NE和白细胞介素-8（IL-8）的体外和体内作用。在治疗的前6天对CF患者评估rhDNase的急性作用。对接受rhDNase治疗超过6个月的稳定CF患者评估中期作用。定期收集痰液样本，通过荧光测定法测量NE活性，通过放射免疫测定法测量IL-8。体外添加rhDNase导致蛋白酶活性增加两倍，这反映在开始使用rhDNase治疗时的急性短暂升高。中期治疗与NE活性和IL-8的下降有关。这些体内结果令人鼓舞，因为蛋白酶活性的增加是短暂的，并且6个月内的趋势是两种炎症标志物均下降。
