Maruna P, Gürlich R, Frasko R, Chachkhiani I, Marunová M, Owen K, Pesková M
Ustav patologické fyziologie 1. lékarské fakulty Univerzity Karlovy, U nemocnice 5, 128 53 Praha 2, Czech Republic.
Sb Lek. 2002;103(2):273-82.
The common basis of systemic inflammatory response to surgical trauma is the activation of cytokine cascade, accompanied by the release of soluble cytokine receptors. The main cytokine axis stimulates the release of acute phase proteins (APP) form liver, modulates metabolic pathways and hormonal responses. The aim of this study was to assess characteristic changes in levels of pro- and anti-inflammatory cytokines in early post-op stages after a major intraabdominal surgery and to compare the results with dynamic changes in APP levels. The results will form a basis of evaluation of diagnostic value of certain cytokines and APP in post-operative complications.
Subjects fell into three categories: 1--patients after colonic resection for colorectal carcinoma I. and II. grade (N = 20), 2--patients after hemipancreatoduodenectomia (N = 17) and 3--control group of 18 healthy subjects. The levels of following parameters were measured between from one day before to three days after surgery: tumour necrosis factor-alpha, interleukin (IL)-1 beta, IL-1ra, IL-2, IL-6, IL-8, IL-10, soluble IL-2 receptors, C reactive protein (CRP) and alpha1-antitrypsin (AAT).
Measured parameters exhibited different dynamic changes in reaction to surgical trauma, according to their roles in immune reaction. Main pro-inflammatory cytokines culminated within 24 hours from the onset of surgery, marked elevations were noted in IL-1ra and the soluble IL-2 receptor. Both measured APP were rising until he 72nd hour post surgery, and their rise was markedly delayed compared to cytokines. The extent of immune reaction as measured by the amplitude of changes in both types of surgery was similar in most measured parameters, apart from marked difference in IL-2R. We also noted significant correlation of plasma levels of IL-6 and IL-1ra.
Surgical trauma as any other significant painful stimulus activates the pro-inflammatory cytokine axis with secondary response of APP. The release or pro-inflammatory cytokines, i.e. TNF-alpha, IL-1, IL-6 and IL-8 is synchronized with the release of antagonistic mediators (i.e. IL-1ra, IL-10, IL-2 and IL-6 soluble receptors), who precede the acceleration of APP production and thus modulate its extent. The evaluation of relationships between pro- and anti-inflammatory factors with regard to prognosis is confounded by unclear interpretation of their changes. The maximum effect of cytokines takes place at local autocrine and paracrine level and systemic levels do not reflect this. This is how we explain minimal changes in plasma levels of IL-1 beta and IL-2, despite their key role as initiators of cytokine cascade. In order to increase their diagnostic value the use a series of measurements is advocated in combination with other clinical and laboratory parameters of inflammation, such as the levels of acute phase proteins.
手术创伤引发全身炎症反应的共同基础是细胞因子级联反应的激活，同时伴有可溶性细胞因子受体的释放。主要的细胞因子轴刺激肝脏释放急性期蛋白（APP），调节代谢途径和激素反应。本研究的目的是评估腹部大手术后早期阶段促炎和抗炎细胞因子水平的特征性变化，并将结果与APP水平的动态变化进行比较。这些结果将为评估某些细胞因子和APP在术后并发症中的诊断价值奠定基础。
研究对象分为三类：1. Ⅰ、Ⅱ期结肠癌结肠切除术后患者（N = 20）；2. 半胰十二指肠切除术后患者（N = 17）；3. 18名健康受试者组成的对照组。在手术前一天至手术后三天期间测量以下参数水平：肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-1受体拮抗剂（IL-1ra）、IL-2、IL-6、IL-8、IL-10、可溶性IL-2受体、C反应蛋白（CRP）和α1-抗胰蛋白酶（AAT）。
根据所测参数在免疫反应中的作用，它们在对手术创伤的反应中呈现出不同的动态变化。主要促炎细胞因子在手术开始后24小时内达到峰值，IL-1ra和可溶性IL-2受体有明显升高。两种所测APP在术后72小时内持续升高，与细胞因子相比，其升高明显延迟。除IL-2R有明显差异外，大多数所测参数中，两种手术类型变化幅度所衡量的免疫反应程度相似。我们还注意到血浆中IL-6和IL-1ra水平存在显著相关性。
手术创伤如同其他任何重大疼痛刺激一样，激活促炎细胞因子轴并引发APP的继发反应。促炎细胞因子即肿瘤坏死因子-α、IL-1、IL-6和IL-8的释放与拮抗介质（即IL-1ra、IL-10、IL-2和IL-6可溶性受体）的释放同步，这些拮抗介质先于APP产生加速并调节其程度。促炎和抗炎因子变化的不明确解释混淆了对其与预后关系的评估。细胞因子的最大作用发生在局部自分泌和旁分泌水平，而全身水平并未反映这一点。这就是尽管IL-1β和IL-2作为细胞因子级联反应的启动因子起关键作用，但血浆水平变化却极小的原因。为提高其诊断价值，提倡结合炎症的其他临床和实验室参数（如急性期蛋白水平）进行一系列测量。
