Meldrum D R, Shames B D, Meng X, Fullerton D A, McIntyre R C, Grover F L, Harken A H
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Ann Thorac Surg. 1998 Aug;66(2):313-7. doi: 10.1016/s0003-4975(98)00525-6.
Inflammatory cytokine production contributes to lung injury after lung ischemia reperfusion and during lung transplant rejection. Although nitric oxide has been demonstrated to reduce lung injury associated with the adult respiratory distress syndrome, it remains unknown whether the mechanism of nitric oxide's beneficial effects involves reducing lung macrophage inflammatory cytokine production. The purpose of this study was to determine whether nitric oxide downregulates lung macrophage inflammatory cytokine production.
Lung macrophages were harvested by bronchoalveolar lavage (10(6) macrophage per milliliter from normal Sprague-Dawley rats, 6 animals per group) and treated under ex vivo tissue culture conditions with the nitric oxide releasing compound S-nitoso-N-acetyl-D, L-penicillamine (0, 10(-5) 10(-4), 10(-3), 10(-2) mol/L) before induction of inflammatory cytokines with endotoxin, (50 ng/mL for 24 hours). Supernatants were assayed for inflammatory cytokine production (tumor necrosis factor alpha, interleukin-1beta) by enzyme-linked immunosorbent assay.
Continuous nitric oxide release by S-nitoso-N-acetyl-D, L-penicillamine decreased lung macrophage tumor necrosis factor-alpha and interleukin-1beta production in a dose-dependent fashion (6 rats per group; data were analyzed for significance [p < 0.05] using two-way analysis of variance with Tukey's post-hoc correction).
Nitric oxide decreases inflammatory cytokine production by lung macrophage. The mechanism of nitric oxide's beneficial effects may be partially attributable to decreased production of inflammatory cytokines. Nitric oxide may serve an expanded role for reducing inflammatory cytokine production during acute lung injury, ischemia-reperfusion-induced inflammation, or lung transplant rejection.
炎症细胞因子的产生在肺缺血再灌注后以及肺移植排斥反应期间会导致肺损伤。尽管一氧化氮已被证明可减轻与成人呼吸窘迫综合征相关的肺损伤，但一氧化氮有益作用的机制是否涉及减少肺巨噬细胞炎症细胞因子的产生仍不清楚。本研究的目的是确定一氧化氮是否下调肺巨噬细胞炎症细胞因子的产生。
通过支气管肺泡灌洗收集肺巨噬细胞（来自正常Sprague-Dawley大鼠，每毫升10⁶个巨噬细胞，每组6只动物），并在体外组织培养条件下用释放一氧化氮的化合物S-亚硝基-N-乙酰-D，L-青霉胺（0、10⁻⁵、10⁻⁴、10⁻³、10⁻²mol/L）处理，然后用内毒素（50 ng/mL，处理24小时）诱导炎症细胞因子。通过酶联免疫吸附测定法检测上清液中炎症细胞因子的产生（肿瘤坏死因子α、白细胞介素-1β）。
S-亚硝基-N-乙酰-D，L-青霉胺持续释放一氧化氮以剂量依赖的方式降低了肺巨噬细胞肿瘤坏死因子-α和白细胞介素-1β的产生（每组6只大鼠；使用带有Tukey事后校正的双向方差分析对数据进行显著性分析[p<0.05]）。
一氧化氮可降低肺巨噬细胞炎症细胞因子的产生。一氧化氮有益作用的机制可能部分归因于炎症细胞因子产生的减少。在急性肺损伤、缺血再灌注诱导的炎症或肺移植排斥反应期间，一氧化氮可能在减少炎症细胞因子产生方面发挥更大的作用。
