Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages.

Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages.
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合成表面活性剂 (Exosurf) 抑制人肺泡巨噬细胞内毒素刺激的细胞因子分泌。

DOI:
10.1165/ajrcmb/7.3.257
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发表时间:
1992
影响因子:
6.4
通讯作者:
Wiedemann,HP
Wiedemann,HP
中科院分区:
医学1区
文献类型:
--
作者:
Thomassen,MJ;Meeker,DP;Antal,JM;Connors,MJ;Wiedemann,HP

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肿瘤坏死因子-α(TNF)、白细胞介素-1,8(IL-1)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)是由肺泡巨噬细胞(AM)产生的炎性细胞因子,并与脓毒症相关的成人呼吸窘迫综合征(ARDS)有关。来自临床试验的初步发现表明,合成表面活性剂Exosurf(Burroughs Wellcome Co.)降低脓毒症诱导的ARDS患者的死亡率。本研究的目的是检测Exosurf对体外AM分泌炎性细胞因子的影响。AM从正常的不吸烟的成年志愿者获得。用酶联免疫法检测AM培养24 h后分泌的TNF、IL-1、IL-6和IL-8。Exosurf以剂量依赖性方式抑制LPS刺激的TNF、IL-1和IL-6分泌。在这些条件下,IL-8分泌不受Exosurf影响。然而,如果AM在培养基中预孵育24小时,然后LPS刺激,则Exosurf抑制IL-8分泌。IL-8产生的调节可不同于TNF、IL-1和IL-6。未受刺激的细胞因子分泌不受任何Exosurf测试浓度的影响。Exosurf对内毒素诱导的人AM细胞因子分泌的抑制作用表明Exosurf可调节肺中炎性细胞因子的产生。新生儿呼吸窘迫综合征的表面活性剂替代治疗可降低发病率和死亡率(1-4)。最近对合成表面活性剂Exosurf的初步研究也显示了与脓毒症相关的成人呼吸窘迫综合征(ARDS)相关的死亡率明显下降的趋势(5)。炎性细胞因子如肿瘤坏死因子-α(TNF)、白细胞介素-1,8(IL-1)和白细胞介素-6(IL-6)已涉及脓毒症和ARDS的发病机制(6-13)。由于中性粒细胞在ARDS的发展中起着重要作用(14),因此白细胞介素-8(IL-8;中性粒细胞趋化因子)也参与其中。以前的研究表明,脂多糖(LPS)刺激的单核细胞TNF分泌,
Tumor necrosis factor-a (TNF), interleukin-l, 8 (IL-l), interleukin-6 (IL-6), and interleukin-8 (IL-8) are inflammatory cytokines produced by alveolar macrophages (AMs) and implicated in sepsis-related adult respiratory distress syndrome (ARDS). Preliminary findings from clinical trials suggest that aerosolized delivery of the synthetic surfactant Exosurf (Burroughs Wellcome Co.) reduces mortality in patients with sepsis-induced ARDS. The purpose of the present study was to examine the effectof Exosurf on inflammatory cytokine secretion from AMs in vitro. AMs were obtained from normal nonsmoking adult volunteers. Secreted TNF, IL-l, IL-6, and IL-8 were measured by enzyme-linked immunoassays in 24 h culture fluids of AMs. Exosurf inhibited LPS-stimulated TNF, IL-l, and IL-6 secretion in a dose-dependent fashion. IL-8 secretion was not affected by Exosurf under these conditions. However, if AMs were preincubated for 24 h in media and then LPS-stimulated, IL-8 secretion was inhibited by Exosurf. Regulation of IL-8 production may differ from TNF, IL-l, and IL-6. Unstimulated cytokine secretion was not affected by any of the tested concentrations of Exosurf. The inhibitory effect of Exosurf on endotoxin-induced cytokine secretion by human AMs suggeststhat Exosurf may modulate inflammatory cytokine production in the lung.Surfactant replacement therapy in neonatal respiratory distress syndrome reduces morbidity and mortality (1-4). Recent preliminary studies with the synthetic surfactant Exosurf have also shown an apparent trend toward reduction in the mortality associated with sepsis-related adult respiratory distress syndrome (ARDS)(5). Inflammatory cytokines such as tumor necrosis factor-a (TNF), interleukin-l, 8 (IL-l), and interleukin-6 (IL-6) have been implicated in the pathogenesis of sepsis and ARDS (6-13). Since the neutrophil plays a prominent role in the development of ARDS (14), interleukin-8 (IL-8; neutrophil chemotactic factor) has also been implicated. A previous study demonstrated that lipopolysaccharide (LPS)-stimulated monocyte TNF secretion is
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