术后免疫抑制的特征可通过γ干扰素逆转，且与白细胞介素-6通路无关。

Features of Postoperative Immune Suppression Are Reversible With Interferon Gamma and Independent of Interleukin-6 Pathways.

作者信息

Longbottom E Rebecca, Torrance Hew D T, Owen Helen C, Fragkou Paraskevi C, Hinds Charles J, Pearse Rupert M, O'Dwyer Michael J

机构信息

*Adult Critical Care Unit, Royal London Hospital, Barts Health NHS Trust, London, UK†Centre for Translational Medicine & Therapeutics, William Harvey Research Institute Queen Mary University of London, London, UK‡Centre for Trauma Sciences, Blizard Institute, Barts & the London School of Medicine & Dentistry, Queen Mary University of London, London, UK§Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.

出版信息

Ann Surg. 2016 Aug;264(2):370-7. doi: 10.1097/SLA.0000000000001484.

DOI:10.1097/SLA.0000000000001484

PMID:26445474

Abstract

OBJECTIVE

The aim of this study was to evaluate the role of interleukin (IL)-6 pathways in postoperative immune suppression and to assess the reversibility of this phenomenon.

BACKGROUND

The postoperative period is characterized by increased IL-6 production and features of immune suppression. In vitro, IL-6 mediates anti-inflammatory effects through inhibition of interferon gamma (IFN-γ) pathways. The significance of the immunomodulatory effects of IL-6 in the clinical setting of postoperative immune suppression remains unclear.

METHODS

Patients over 45 years old undergoing elective surgery, involving the gastrointestinal tract, were recruited. IL-6 levels were assayed using an enzyme linked immunosorbent assay preoperatively, and at 24 and 48 hours. Peripheral blood mononuclear cells from healthy volunteers were cultured in perioperative serum and CD14Human Leukocyte Antigen-DR (HLA-DR) [monocyte HLA-DR (mHLA-DR)] geometric mean florescent intensity was measured in the presence and absence of IL-6 neutralizing antibody and recombinant IFN-γ.

RESULTS

Of the 108 patients, 41 developed a postoperative infection. The IL-6 levels increased 19-fold from the preoperative sample to 24 hours postoperatively (P < 0.0001). Higher IL-6 levels at 24 (P = 0.0002) and 48 hours (P = 0.003) were associated with subsequent postoperative infectious complications. mHLA-DR mean florescent intensity fell when healthy peripheral blood mononuclear cells were cultured with postoperative serum compared with preoperative serum (P = 0.008). This decrease was prevented by the presence of IFN-γ in the culture media, but not by the presence of IL-6-neutralizing antibody.

CONCLUSIONS

IL-6 levels increase after a major surgery and are associated with an increased susceptibility to postoperative infections. Serum obtained from postoperative patients induces an immunosuppressive response, reflected in reduced mHLA-DR levels, mediated through IL-6 independent pathways and is reversible with IFN-γ. These data may have therapeutic implications for the prevention of infection in patients undergoing major surgery.

摘要

目的

本研究旨在评估白介素（IL）-6通路在术后免疫抑制中的作用，并评估这种现象的可逆性。

背景

术后阶段的特点是IL-6产生增加和免疫抑制特征。在体外，IL-6通过抑制干扰素γ（IFN-γ）通路介导抗炎作用。IL-6在术后免疫抑制临床环境中的免疫调节作用的意义仍不清楚。

方法

招募45岁以上接受择期手术（涉及胃肠道）的患者。术前、术后24小时和48小时使用酶联免疫吸附测定法检测IL-6水平。将健康志愿者的外周血单个核细胞在围手术期血清中培养，并在存在和不存在IL-6中和抗体及重组IFN-γ的情况下测量CD14人白细胞抗原-DR（HLA-DR）[单核细胞HLA-DR（mHLA-DR）]几何平均荧光强度。

结果

108例患者中，41例发生术后感染。IL-6水平从术前样本到术后24小时增加了19倍（P<0.0001）。术后24小时（P = 0.0002）和48小时（P = 0.003）较高的IL-6水平与随后的术后感染并发症相关。与术前血清相比，当健康外周血单个核细胞与术后血清一起培养时，mHLA-DR平均荧光强度下降（P = 0.008）。培养基中存在IFN-γ可防止这种下降，但IL-6中和抗体则不能。