Interleukin-18 restores immune suppression in patients with nonseptic surgery, but not with sepsis
Interleukin-18 restores immune suppression in patients with nonseptic surgery, but not with sepsis
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DOI：
10.1016/j.amjsurg.2006.10.021
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发表时间：
2007-06-01
影响因子：
3
通讯作者：
Mochizuki, Hidetaka
中科院分区：
文献类型：
--
作者：
Hiraki, Shuhichi;Ono, Satoshi;Mochizuki, Hidetaka
背景：我们研究了脓毒症和非脓毒症手术应激患者外周血单核细胞 (PBMC) 的细胞免疫反应，特别是干扰素 γ (IFN-gamma) 的产生，重点关注白细胞介素 (IL)-18 及其受体 (IL-18R)。方法：32 名接受择期手术的消化道癌患者 (OP) 和 26 名患有腹膜炎的脓毒症患者 (SP) 参加了这项研究。 OP组在术后第一天（POD1）、POD5、POD10和POD15采血，SP组在急诊入院时采血。十名健康志愿者作为对照。在抗 CD3 抗体或 IL-2 和 IL-12 存在下培养 PBMC，有或没有额外的 IL-18 刺激，以测量 IFN-γ 的产生。通过流式细胞术评估CD56（+）NK（自然杀伤）细胞上IL-18R的表达。结果：与健康组相比，OP（POD5）和SP组中PBMCs的IL-2和IL-12诱导的IFN-γ产生均显着受到抑制。控制。有趣的是，额外的 IL-18 刺激上调了 OP 组和对照组 PBMC 的 IFN-γ 产生，但在 SP 组中则不然。 CD56(+) NK细胞上IL-18R的表达在OP组和对照组中保持一致，但在SP组中下降。结论：在脓毒症患者和接受择期手术的患者的PBMC中，细胞因子（IL-2和IL-12）诱导的IFN-γ产生受到抑制。然而，脓毒症患者和非脓毒症手术应激患者CD56(+) NK细胞上IL-18R的表达不同。我们的结果表明，外源性 IL-18 给药可能可以有效预防非脓毒症择期手术患者的免疫抑制。 (C) 2007 Excerpta Medica Inc. 保留所有权利。
Background: We investigated cellular immune responses, in particular interferon gamma (IFN-gamma) production, by peripheral blood mononuclear cells (PBMCs) in patients with septic and nonseptic surgical stress, focusing on interleukin (IL)-18 and its receptor (IL-18R).Methods: Thirty-two patients with alimentary tract carcinoma who underwent elective surgery (OP) and 26 septic patients (SP) with peritonitis were enrolled in this study. Blood was collected on the first postoperative day (POD1), POD5, POD10, and POD15 in the OP group and on the emergency admission in the SP group. Ten healthy volunteers served as controls. PBMCs were cultured in the presence of anti-CD3 antibody or IL-2 and IL-12, with or without additional IL-18 stimulation, to measure IFN-gamma production. IL-18R expression on CD56(+) NK (natural killer) cells was evaluated by flow cytometry.Results: IL-2- and IL- 12-induced IFN-gamma production by PBMCs was suppressed significantly in both the OP (POD5) and SP groups compared with that in healthy. controls. Interestingly, additional IL-18 stimulation up-regulated IFN-gamma production by PBMCs in the OP group as well as the control group, but not in the SP group. IL-18R expression on CD56(+) NK cells was maintained consistently in the OP group as well as the control group, but decreased in the SP group.Conclusions: IFN-gamma production induced by cytokines (IL-2 and IL-12) was suppressed in PBMCs from both patients with sepsis and those who had undergone elective surgery. However, IL- 18R expression on CD56(+) NK cells was different between patients with sepsis and nonseptic surgical stress. Our results suggest that exogenous IL-18 administration may be effective in preventing immune suppression in patients with nonseptic elective surgery. (C) 2007 Excerpta Medica Inc. All rights reserved.