Allen J N, Moore S A, Pope-Harman A L, Marsh C B, Wewers M D
Ohio State University Medical Center, Division of Pulmonary and Critical Care Medicine, Columbus 43210.
J Lab Clin Med. 1995 Mar;125(3):356-69.
Alveolar macrophages have been shown to be major producers of the potent proinflammatory cytokines interleukin-1 beta and tumor necrosis factor-alpha, and of the antiinflammatory cytokine interleukin-1 receptor antagonist. During the adult respiratory distress syndrome the normally surfactant-coated alveolus becomes flooded with plasma proteins, altering the milieu of alveolar cells such as alveolar macrophages. To understand alveolar macrophage function during the adult respiratory distress syndrome, the individual and combined effects of surfactant and plasma on alveolar macrophage cytokine production was examined. A synthetic surfactant (Exosurf) and a bovine-derived surfactant (Survanta) both inhibited production of interleukin-1 beta, pro-interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-1 receptor antagonist in a dose-dependent manner. This inhibition was noted when both endotoxin and heat-killed Staphylococcus aureus were used as stimuli. Autologous plasma also inhibited interleukin-1 beta and tumor necrosis factor-alpha release in a dose-dependent manner, but, unlike surfactant, plasma did not inhibit interleukin-1 receptor antagonist release. Similarly, the combination of plasma and surfactant inhibited interleukin-1 beta and tumor necrosis factor-alpha release but not interleukin-1 receptor antagonist release. In support of these data, interleukin-1 receptor antagonist was detectable in five of six bronchoalveolar lavage fluid samples from patients with adult respiratory distress syndrome at a mean concentration of 465 pg/ml; on the other hand, interleukin-1 beta was not detectable in any of these samples. These results indicate that the relative production of interleukin-1 beta, tumor necrosis factor-alpha, and interleukin-1 receptor antagonist can be altered depending on the local concentration of both surfactant and plasma.
肺泡巨噬细胞已被证明是强效促炎细胞因子白细胞介素 -1β和肿瘤坏死因子 -α以及抗炎细胞因子白细胞介素 -1受体拮抗剂的主要产生者。在成人呼吸窘迫综合征期间，正常情况下被表面活性剂覆盖的肺泡会充满血浆蛋白，从而改变肺泡细胞（如肺泡巨噬细胞）的微环境。为了解成人呼吸窘迫综合征期间肺泡巨噬细胞的功能，研究了表面活性剂和血浆对肺泡巨噬细胞细胞因子产生的单独及联合作用。一种合成表面活性剂（Exosurf）和一种牛源性表面活性剂（Survanta）均以剂量依赖性方式抑制白细胞介素 -1β、前白细胞介素 -1β、肿瘤坏死因子 -α和白细胞介素 -1受体拮抗剂的产生。当使用内毒素和热灭活金黄色葡萄球菌作为刺激物时，均观察到这种抑制作用。自体血浆也以剂量依赖性方式抑制白细胞介素 -1β和肿瘤坏死因子 -α的释放，但与表面活性剂不同，血浆不抑制白细胞介素 -1受体拮抗剂的释放。同样，血浆和表面活性剂的组合抑制白细胞介素 -1β和肿瘤坏死因子 -α的释放，但不抑制白细胞介素 -1受体拮抗剂的释放。为支持这些数据，在成人呼吸窘迫综合征患者的六份支气管肺泡灌洗 fluid 样本中的五份中可检测到白细胞介素 -1受体拮抗剂，平均浓度为 465 pg/ml；另一方面，在这些样本中均未检测到白细胞介素 -1β。这些结果表明，白细胞介素 -1β、肿瘤坏死因子 -α和白细胞介素 -1受体拮抗剂的相对产生可根据表面活性剂和血浆的局部浓度而改变。
