Differential regulation of systemic IL-18 and IL-12 release during postoperative sepsis: High serum IL-18 as an early predictive indicator of lethal outcome

Differential regulation of systemic IL-18 and IL-12 release during postoperative sepsis: High serum IL-18 as an early predictive indicator of lethal outcome
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DOI:
10.1097/00024382-200210000-00002
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发表时间:
2002-10-01
期刊:
影响因子:
3.1
通讯作者:
Holzmann, B
Holzmann, B
中科院分区:
医学2区
文献类型:
--
作者:
Emmanuilidis, K;Weighardt, H;Holzmann, B

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对 66 名术后脓毒症患者(38 名幸存者和 28 名非幸存者)随时间的推移测量了关键免疫调节细胞因子 IL-12 和 IL-18 的全身水平。脓毒症死亡率与任何检查的临床参数(包括年龄、性别、基础疾病和外科手术)均没有显着相关性。细胞因子水平分析显示,在整个观察期间,与无脓毒症的对照手术患者相比,脓毒症患者的IL-12显着降低。脓毒症幸存者和非幸存者之间的 IL-12 血清水平没有显着差异。与 IL-12 相比,存活和死亡脓毒症患者的 IL-18 血清水平均显着高于对照组。重要的是,我们还观察到,在研究的所有时间点(包括脓毒症诊断后的第 1 天),与脓毒症幸存者相比,致命性脓毒症患者的 IL-18 水平显着升高。 IL-18 水平在致死性脓毒症过程中显着升高,但在脓毒症幸存者中仍保持在相当水平。对脓毒症第 1 天或第 2 天测量的 IL-18 值进行逻辑回归分析表明,高血清 IL-18 代表术后脓毒症致死结果的早期预测因素。与之前在小鼠模型中的研究结果一致,我们的结果表明,IL-12 可能有助于针对脓毒症攻击的保护性免疫反应,而 IL-18 可能优先促进器官损伤和致命性休克。
Systemic levels of the key immune regulatory cytokines IL-12 and IL-18 were measured over time in 66 patients with postoperative sepsis (38 survivors and 28 nonsurvivors). Sepsis mortality was not significantly associated with any of the clinical parameters examined, including age, gender, underlying disease, and surgical procedure. Analysis of cytokine levels showed that during the entire observation period, IL-12 was significantly reduced in sepsis patients compared with control surgical patients without sepsis. IL-12 serum levels did not significantly differ between sepsis survivors and nonsurvivors. In contrast to IL-12, IL-18 serum levels were significantly higher in both surviving and nonsurviving sepsis patients than in controls. Importantly, we also observed that IL-18 levels were significantly increased in patients with lethal sepsis compared with sepsis survivors at all time points studied, including day 1 after sepsis diagnosis. IL-18 levels were significantly increased during the course of lethal sepsis, but remained at a comparable level in sepsis survivors. Logistic regression analysis of IL-18 values measured on days 1 or 2 of sepsis revealed that high serum IL-18 represents an early predictive factor for the lethal outcome of postoperative sepsis. Consistent with previous work in mouse models, our results suggest that IL-12 may contribute to protective immune reactions against a septic challenge, whereas IL-18 may preferentially promote organ injury and lethal shock.