Lendemans Sven, Kreuzfelder Ernst, Rani Meenakshi, Bayeeh Emilie, Schade F Ulrich, Flohé Stefanie B, Waydhas Christian, Flohé Sascha
Department of Trauma Surgery, University Hospital of Essen, Essen, Germany.
J Trauma. 2007 Oct;63(4):740-6. doi: 10.1097/01.ta.0000240451.42238.d1.
Severe injury after trauma is associated with a diminished production of different proinflammatory cytokines after stimulation with bacterial cell wall components. The cellular mechanisms, leading to a decreased responsiveness especially of monocytes after multiple injuries have not yet been elucidated in detail. The expression of Toll-like receptors (TLR) on leukocytes is essential for recognition of bacterial components. We investigated the expression of TLR2 and 4 in correlation with gram-negative and gram-positive stimuli-dependent cytokine liberation after severe injury in comparison with that in healthy volunteers.
In a prospective clinical experimental study, 12 trauma patients with an Injury Severity Score above 21 points and 14 healthy volunteers were analyzed. Heparinized whole blood samples of patients were collected within 48 hours after trauma and incubated in vitro with or without lipopolysaccharide (LPS) and peptidoglycan (PGN). TLR2 and TLR4 expression on monocytes was analyzed by flow cytometry. LPS- and PGN-induced tumor necrosis factor alpha (TNFalpha) and interleukin-8 production was measured by means of enzyme-linked immunosorbent assay.
Both LPS- and PGN-induced TNFalpha liberation were significantly reduced in severely injured patients. The surface expression of TLR2 was also significantly decreased on monocytes collected from trauma patients, whereas the expression of TLR4 remained unchanged. There was only a negative correlation between TLR2 expression and the liberation of TNFalpha after stimulation with LPS or PGN.
We conclude that diminished cytokine production after trauma cannot be explained simply by changes in TLR2 or TLR4 expression and that subsequent signaling cascades or additional receptors are involved in the blunted cytokine response after trauma.
创伤后的严重损伤与细菌细胞壁成分刺激后不同促炎细胞因子的产生减少有关。导致尤其是单核细胞在多处损伤后反应性降低的细胞机制尚未得到详细阐明。白细胞上Toll样受体（TLR）的表达对于识别细菌成分至关重要。我们研究了与健康志愿者相比，严重损伤后TLR2和TLR4的表达与革兰氏阴性和革兰氏阳性刺激依赖性细胞因子释放的相关性。
在一项前瞻性临床实验研究中，分析了12名损伤严重度评分高于21分的创伤患者和14名健康志愿者。在创伤后48小时内收集患者的肝素化全血样本，并在体外与或不与脂多糖（LPS）和肽聚糖（PGN）一起孵育。通过流式细胞术分析单核细胞上TLR2和TLR4的表达。通过酶联免疫吸附测定法测量LPS和PGN诱导的肿瘤坏死因子α（TNFα）和白细胞介素-8的产生。
严重受伤患者中，LPS和PGN诱导的TNFα释放均显著降低。从创伤患者收集的单核细胞上TLR2的表面表达也显著降低，而TLR4的表达保持不变。在用LPS或PGN刺激后，TLR2表达与TNFα释放之间仅存在负相关。
我们得出结论，创伤后细胞因子产生减少不能简单地用TLR2或TLR4表达的变化来解释，并且随后的信号级联反应或其他受体参与了创伤后细胞因子反应减弱的过程。
