Gaïni S, Pedersen S S, Koldkaer O G, Pedersen C, Moestrup S K, Møller H J
Department of Infectious Diseases, Odense University Hospital, Odense, Denmark.
Clin Exp Immunol. 2008 Mar;151(3):423-31. doi: 10.1111/j.1365-2249.2007.03586.x. Epub 2008 Jan 8.
High mobility group-box 1 protein (HMGB1) is a late-onset proinflammatory cytokine. Soluble haemoglobin scavenger receptor (sCD163) is a specific marker of anti-inflammatory macrophages. The study purpose was to relate the levels of these new markers in bactaeremic patients to levels of well-known pro- and anti-inflammatory markers [procalcitonin, lipopolysaccharide (LPS)-binding protein, interleukin (IL)-6, IL-10] and to evaluate the levels in relation to disease severity and aetiology. A total of 110 patients with bacteraemia were included in a prospective manner from the medical department at a large Danish university hospital. Levels of HMGB1 and sCD163 were higher in patients with bacteraemia compared to controls (P < 0.001). HMGB1 correlated with proinflammatory molecules [procalcitonin (PCT)] and traditional infectious parameters [C-reactive proteins (CRP), white blood cells (WBC) and neutrophils], whereas sCD163 correlated with levels of IL-6, IL-10 but not to lipopolysaccharide-binding protein (LBP), PCT or CRP. Levels of sCD163 and IL-6 were significantly higher among non-survivors compared to survivors (P < 0.05). Neither HMGB1 nor any of the proinflammatory markers were elevated in fatal cases compared to survivors. There was no statistically significant difference in HMGB1 and sCD163 levels in Gram-negative versus Gram-positive bacteraemia. HMGB1 reflects proinflammatory processes, whereas sCD163 reflects anti-inflammatory processes as judged by correlations with traditional marker molecules. sCD163 and IL-6, but not HMGB1, were prognostic markers in this cohort pointing to an anti-inflammatory predominance in patients with fatal disease outcome.
高迁移率族蛋白B1(HMGB1)是一种迟发性促炎细胞因子。可溶性血红蛋白清除受体(sCD163)是抗炎巨噬细胞的特异性标志物。本研究的目的是将菌血症患者中这些新标志物的水平与已知的促炎和抗炎标志物[降钙素原、脂多糖(LPS)结合蛋白、白细胞介素(IL)-6、IL-10]的水平相关联,并评估与疾病严重程度和病因相关的水平。从丹麦一所大型大学医院的内科前瞻性纳入了110例菌血症患者。与对照组相比,菌血症患者的HMGB1和sCD163水平更高(P<0.001)。HMGB1与促炎分子[降钙素原(PCT)]和传统感染参数[C反应蛋白(CRP)、白细胞(WBC)和中性粒细胞]相关,而sCD163与IL-6、IL-10水平相关,但与脂多糖结合蛋白(LBP)、PCT或CRP无关。与幸存者相比,非幸存者的sCD163和IL-6水平显著更高(P<0.05)。与幸存者相比,致命病例中HMGB1和任何促炎标志物均未升高。革兰阴性菌血症与革兰阳性菌血症患者的HMGB1和sCD163水平无统计学显著差异。根据与传统标志物分子的相关性判断,HMGB1反映促炎过程,而sCD163反映抗炎过程。在该队列中,sCD163和IL-6而非HMGB1是预后标志物,表明致命疾病结局患者中存在抗炎优势。