Lane S J, Wilkinson J R, Cochrane G M, Lee T H, Arm J P
Department of Allergy and Allied Respiratory Disorders, United Medical School, Guy's Hospital, London, United Kingdom.
Am Rev Respir Dis. 1993 Mar;147(3):690-6. doi: 10.1164/ajrccm/147.3.690.
We previously described a 3 kD neutrophil priming activity (NPA) derived from peripheral blood monocytes that is suppressed by glucocorticoid treatment of monocytes derived from individuals with corticosteroid-sensitive (CS) but not corticosteroid-resistant (CR) asthma. We compared the effects of glucocorticoids on the in vitro generation of other cytokines by monocytes of CS and CR asthmatic individuals. A total of 11 CS and 8 CR asthmatic subjects were studied. Monocytes were cultured overnight in the presence or absence of 5 micrograms/ml of lipopolysaccharide (LPS) with or without hydrocortisone (HC) or dexamethasone. TNF-alpha, IL-1 beta, and GM-CSF were measured by ELISA, mRNA for these cytokines were detected by northern analysis, and NPA was identified by its capacity to enhance ionophore-induced LTB4 generation from neutrophils. In the absence of LPS there was no significant difference in the generation of cytokines between monocytes derived from CS and CR individuals. Treatment of monocytes by 10(-6) M HC suppressed NPA generation from CS (72%, p = 0.002) but not CR subjects (10%, p = 0.47). In contrast there was no effect of glucocorticoids on the generation of other cytokines from monocytes of either CS or CR subjects. In the absence of LPS, mRNA for IL-1 beta and GM-CSF were not detected by northern analysis, and glucocorticoids had no significant effects on mRNA for TNF-alpha in either group. LPS at 5 micrograms/ml enhanced cytokine but not NPA generation and markedly increased cytokine mRNA in monocytes of both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前描述了一种源自外周血单核细胞的3 kD中性粒细胞启动活性（NPA），对来自皮质类固醇敏感（CS）但非皮质类固醇抵抗（CR）哮喘患者的单核细胞进行糖皮质激素处理可抑制该活性。我们比较了糖皮质激素对CS和CR哮喘患者单核细胞体外产生其他细胞因子的影响。共研究了11名CS哮喘患者和8名CR哮喘患者。单核细胞在存在或不存在5微克/毫升脂多糖（LPS）的情况下培养过夜，同时添加或不添加氢化可的松（HC）或地塞米松。通过ELISA检测肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和粒细胞-巨噬细胞集落刺激因子（GM-CSF），通过Northern分析检测这些细胞因子的mRNA，并通过其增强中性粒细胞中离子载体诱导的白三烯B4（LTB4）生成的能力来鉴定NPA。在不存在LPS的情况下，CS和CR个体来源的单核细胞产生细胞因子方面没有显著差异。用10^(-6) M HC处理单核细胞可抑制CS患者的NPA生成（72%，p = 0.002），但对CR患者无抑制作用（10%，p = 0.47）。相比之下，糖皮质激素对CS或CR患者单核细胞产生其他细胞因子没有影响。在不存在LPS的情况下，Northern分析未检测到IL-1β和GM-CSF的mRNA，糖皮质激素对两组中TNF-α的mRNA均无显著影响。5微克/毫升的LPS增强了细胞因子的产生，但未增强NPA的产生，并显著增加了两组单核细胞中细胞因子的mRNA。（摘要截短至250字）
