Department of Internal Medicine, Slotervaart Hospital, Amsterdam, The Netherlands.
PLoS Negl Trop Dis. 2009 Jun 2;3(6):e453. doi: 10.1371/journal.pntd.0000453.
Severe leptospirosis features bleeding and multi-organ failure, leading to shock and death. Currently it is assumed that both exaggerated inflammation and immune suppression contribute to mortality in sepsis. Indeed, several proinflammatory cytokines are reported to be induced during leptospirosis. Toll-like receptors, which play an important role in the initiation of an innate immune response, are inhibited by negative regulators including the membrane-bound ST2 (mST2) receptor. Soluble ST2 (sST2) has been implicated to inhibit signaling through mST2. The aim of this study was to determine the extent of sST2 and (pro-) inflammatory cytokine release in patients with severe leptospirosis.
In an observational study, 68 consecutive cases of severe leptospirosis were included. Soluble ST2 and cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10) were repeatedly measured. To determine whether blood cells are a source of sST2 during infection, we undertook an in vitro experiment: human whole blood and peripheral blood mononuclear cells (PBMC) were stimulated with viable pathogenic Leptospira. All patients showed elevated sST2, IL-6, IL-8, and IL-10 levels on admission. Admission sST2 levels correlated with IL-6, IL-8, and IL-10. Thirty-four patients (50%) showed clinical bleeding. Soluble ST2 levels were significantly associated with bleeding overall (OR 2.0; 95%CI: 1.2-3.6) and severe bleeding (OR 5.1; 95%CI: 1.1-23.8). This association was unique, since none of the cytokines showed this correlation. Moreover, sST2 was associated with mortality (OR 2.4; 95%CI: 1.0-5.8). When either whole blood or isolated PBMCs were stimulated with Leptospira in vitro, no sST2 production could be detected.
Patients with severe leptospirosis demonstrated elevated plasma sST2 levels. Soluble ST2 levels were associated with bleeding and mortality. In vitro experiments showed that (white) blood cells are probably not the source. In this regard, sST2 could be an indicative marker for tissue damage in patients suffering from severe leptospirosis.
严重的钩端螺旋体病具有出血和多器官衰竭的特征，导致休克和死亡。目前认为，在脓毒症中，过度的炎症和免疫抑制都会导致死亡率升高。事实上，有报道称在钩端螺旋体病中会诱导几种促炎细胞因子。 Toll 样受体在先天免疫反应的启动中发挥重要作用，受负调节剂（包括膜结合 ST2(mST2)受体）的抑制。可溶性 ST2(sST2)被认为可以抑制 mST2 的信号传导。本研究旨在确定严重钩端螺旋体病患者中 sST2 和（前）炎症细胞因子释放的程度。
在一项观察性研究中，纳入了 68 例连续的严重钩端螺旋体病患者。反复测量可溶性 ST2 和细胞因子（TNF-α、IL-1β、IL-6、IL-8 和 IL-10）。为了确定在感染过程中血细胞是否是 sST2 的来源，我们进行了一项体外实验：用致病性活 Leptospira 刺激人全血和外周血单核细胞（PBMC）。所有患者在入院时均显示 sST2、IL-6、IL-8 和 IL-10 水平升高。入院时 sST2 水平与 IL-6、IL-8 和 IL-10 相关。34 例患者（50%）出现临床出血。可溶性 ST2 水平与总体出血（OR 2.0；95%CI：1.2-3.6）和严重出血（OR 5.1；95%CI：1.1-23.8）显著相关。这种相关性是独特的，因为没有一种细胞因子显示出这种相关性。此外，sST2 与死亡率相关（OR 2.4；95%CI：1.0-5.8）。当体外用 Leptospira 刺激全血或分离的 PBMC 时，未检测到 sST2 的产生。
严重钩端螺旋体病患者显示出升高的血浆 sST2 水平。可溶性 ST2 水平与出血和死亡率相关。体外实验表明，（白细胞）血细胞可能不是来源。在这方面，sST2 可能是严重钩端螺旋体病患者组织损伤的指示性标志物。
