Endotoxin and IL-1 hyporesponsiveness in a patient with recurrent bacterial infections.
Endotoxin and IL-1 hyporesponsiveness in a patient with recurrent bacterial infections.
复制标题
反复细菌感染患者的内毒素和 IL-1 反应低下。
DOI：
10.4049/jimmunol.158.8.3959
复制
发表时间：
1997
影响因子：
4.4
通讯作者：
J. I. Gallin
中科院分区：
文献类型：
--
作者：
D. Kuhns;D. L. Priel;J. I. Gallin
我们描述了一个15岁的女孩与复发性细菌感染谁是难治性的影响LPS在体内和体外和IL-1在体外。大肠埃希菌内毒素静脉内激发患者引起低于正常的发热反应，循环中性粒细胞数量几乎没有变化，TNF-α、IL-6、IL-8、乳铁蛋白和粒细胞CSF的血浆水平低于正常水平;但是，诱导了抗炎介质IL-1受体拮抗剂和可溶性TNF受体（60 kDa）的正常水平。体外研究表明，患者的单核细胞表达CD 14（LPS受体），并以特异性方式结合LPS，但在LPS刺激后不能产生TNF-α和粒细胞CSF，也不能对IL-1、热灭活金黄色葡萄球菌和可溶性葡聚糖产生应答。外周血患者的中性粒细胞表现出正常的CD 14表达，但对LPS处理（100-1000 ng/ml，37 ℃，30分钟）没有反应，LPS处理导致表面标志物C10、CD 18、CD 11b、CD 67和CD 45的表达增加，而正常中性粒细胞中L-选择素的表达减少。用FMLP（0.1 μ M）治疗正常和患者中性粒细胞导致这些表面标志物的表达发生等效改变。患者的中性粒细胞不能被LPS或IL-1 β激活以增强FMLP诱导的O2生成，但正常地被TNF-α和血小板活化因子激活。该患者对LPS和IL-1的低反应性很可能是由于信号转导途径的早期缺陷。
We describe a 15-yr-old girl with recurrent bacterial infections who is refractory to the effects of LPS in vivo and in vitro and IL-1 in vitro. Intravenous challenge of the patient with Escherichia coli endotoxin caused a subnormal febrile response, little alteration in the number of circulating neutrophils, and subnormal elevations in the plasma levels of TNF-alpha, IL-6, IL-8, lactoferrin, and granulocyte CSF; however, normal levels of the anti-inflammatory mediators IL-1 receptor antagonist and soluble TNF receptor (60 kDa) were induced. Studies in vitro indicated the patient's monocytes expressed CD14, the LPS receptor, and bound LPS in a specific manner, but failed to produce TNF-alpha and granulocyte CSF after stimulation with LPS, and failed to respond to IL-1, heat-killed Staphylococcus aureus, and soluble glucan. Peripheral blood patient neutrophils exhibited normal expression of CD14, but failed to respond to treatment with LPS (100-1000 ng/ml for 30 min at 37 degrees C), a treatment that caused increased expression of the surface markers, C10, CD18, CD11b, CD67, and CD45, and decreased expression of L-selectin in normal neutrophils. Treatment of normal and patient neutrophils with FMLP (0.1 microM) resulted in equivalent altered expression of these surface markers. Patient neutrophils could not be primed by either LPS or IL-1beta for enhanced FMLP-induced O2- generation, but primed normally to TNF-alpha and platelet-activating factor. This patient's hyporesponsiveness to LPS and IL-1 is most likely due to a defect very early in the signal-transduction pathway.