Powers Kinga A, Woo James, Khadaroo Rachel G, Papia Giuseppe, Kapus Andras, Rotstein Ori D
Department of Surgery, University of Toronto, University Health Network, Toronto General Hospital, Toronto, Canada.
Surgery. 2003 Aug;134(2):312-8. doi: 10.1067/msy.2003.246.
Resuscitated hemorrhagic shock predisposes patients to the development of acute respiratory distress syndrome (ARDS). Hypertonic saline (HTS) has been shown to inhibit immune cell activation in response to lipopolysaccharide (LPS) in vitro and to reduce lung damage when used for resuscitation of hemorrhagic shock in vivo. We hypothesize that HTS resuscitation of hemorrhagic shock may exert this anti-inflammatory effect by modulating alveolar macrophage function leading to an altered balance between the proinflammatory and the counter-inflammatory response.
A 2-hit rat model of shock resuscitation was used. Alveolar macrophages were harvested by bronchoalveolar lavage (BAL), and tumor necrosis factor (TNF)-alpha and interleukin (IL)-10 were quantified in the cell culture supernatants by enzyme-linked immunosorbent assay (ELISA). Alternatively, 1 hour after resuscitation, animals received endotracheal LPS followed by endotracheal anti-IL-10 neutralizing antibody. Lung injury was determined by measuring BAL neutrophil counts 4 hours after LPS in vivo administration.
Systemic administration of HTS significantly modulates the responsiveness of alveolar macrophages. Specifically, HTS resuscitation inhibited LPS-induced TNF-alpha production while enhancing IL-10 release in response to LPS administered ex vivo and in vivo. Anti-IL-10 antibody in vivo partially reversed the lung protective effect of HTS resuscitation.
HTS resuscitation exerts an immunomodulatory effect on alveolar macrophages by shifting the balance of pro- and counter-inflammatory cytokine production in favor of an anti-inflammatory response. The in vivo data suggest a causal role for HTS-induced augmented IL-10 as protective. These findings suggest a novel mechanism for the in vivo salutary effect of HTS resuscitation on lung injury after resuscitated hemorrhagic shock.
复苏后的失血性休克使患者易患急性呼吸窘迫综合征（ARDS）。高渗盐水（HTS）已被证明在体外可抑制免疫细胞对脂多糖（LPS）的激活反应，并在体内用于失血性休克复苏时可减轻肺损伤。我们假设，HTS对失血性休克的复苏可能通过调节肺泡巨噬细胞功能发挥这种抗炎作用，从而导致促炎反应和抗炎反应之间的平衡改变。
采用双打击休克复苏大鼠模型。通过支气管肺泡灌洗（BAL）收集肺泡巨噬细胞，并通过酶联免疫吸附测定（ELISA）对细胞培养上清液中的肿瘤坏死因子（TNF）-α和白细胞介素（IL）-10进行定量分析。另外，复苏1小时后，动物接受气管内注射LPS，随后气管内注射抗IL-10中和抗体。通过在体内给予LPS 4小时后测量BAL中性粒细胞计数来确定肺损伤情况。
全身给予HTS可显著调节肺泡巨噬细胞的反应性。具体而言，HTS复苏抑制了LPS诱导的TNF-α产生，同时增强了对体内外给予LPS的反应中IL-10的释放。体内抗IL-10抗体部分逆转了HTS复苏的肺保护作用。
HTS复苏通过改变促炎和抗炎细胞因子产生的平衡，使其有利于抗炎反应，从而对肺泡巨噬细胞发挥免疫调节作用。体内数据表明，HTS诱导的IL-10增加具有保护作用。这些发现提示了HTS复苏对复苏后失血性休克后肺损伤的体内有益作用的一种新机制。
