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2 型糖尿病与人类内毒素血症中细胞因子反应和黏附分子表达受损有关。

Type 2 diabetes mellitus is associated with impaired cytokine response and adhesion molecule expression in human endotoxemia.

机构信息

Centre of Inflammation and Metabolism, Department of Infectious Diseases, University Hospital Rigshospitalet, Rigshospitalet-M 7641, Blegdamsvej 9, 2100, Copenhagen, Denmark.

出版信息

Intensive Care Med. 2010 Sep;36(9):1548-55. doi: 10.1007/s00134-010-1845-1. Epub 2010 Mar 13.

Abstract

PURPOSE

Type 2 diabetes is associated with an increased risk of acquiring infectious diseases and developing sepsis. This may partly be due to immune dysfunction. We investigated the in vivo innate immune response of type 2 diabetic persons to an intravenous injection of E. coli lipopolysaccharide (LPS).

METHODS

After ethics approval, informed consent and a thorough physical examination, 19 type 2 diabetic patients and 23 healthy controls were included. LPS was given as an intravenous bolus injection of 0.3 ng/kg. Physiological variables, white blood cell count, and plasma concentrations of tumour necrosis factor (TNF), interleukin-6 (IL-6), interleukin-1 receptor antagonist (IL-1ra), and the adhesion molecules E-selectin, vascular adhesion molecule (VCAM)-1, and intracellular adhesion molecule (ICAM)-1 were measured hourly for 8 h.

RESULTS

LPS injection induced a systemic inflammatory response with increases in neutrophils, temperature, heart rate and plasma concentrations of cytokines and adhesion molecules in healthy and type 2 diabetic volunteers. Type 2 diabetes was associated with less pronounced LPS-induced increases in TNF, IL-1ra, VCAM-1 and ICAM-1. There was a trend towards an attenuated upregulation of E-selectin in diabetics, even though the plasma concentration tended to be generally higher compared to healthy controls.

CONCLUSIONS

Patients with type 2 diabetes exhibit an attenuated increase in plasma levels of TNF and IL-1ra, as well as an attenuated upregulation of VCAM-1 and ICAM-1 to LPS in vivo. This finding may provide a mechanistic explanation for the adverse outcome seen during infectious diseases in diabetic patients.

摘要

目的

2 型糖尿病与感染性疾病和脓毒症风险增加有关。这可能部分归因于免疫功能障碍。我们研究了 2 型糖尿病患者对静脉注射大肠杆菌脂多糖(LPS)的体内固有免疫反应。

方法

在获得伦理批准、知情同意和全面体检后,纳入 19 例 2 型糖尿病患者和 23 例健康对照者。LPS 以 0.3ng/kg 的静脉推注给予。生理变量、白细胞计数以及肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、白细胞介素-1 受体拮抗剂(IL-1ra)和粘附分子 E-选择素、血管细胞粘附分子(VCAM)-1 和细胞间粘附分子(ICAM)-1 的血浆浓度在 8 小时内每小时测量一次。

结果

LPS 注射诱导了健康和 2 型糖尿病志愿者的全身炎症反应,导致中性粒细胞、体温、心率和细胞因子及粘附分子的血浆浓度增加。2 型糖尿病与 TNF、IL-1ra、VCAM-1 和 ICAM-1 诱导的增加幅度较小有关。尽管与健康对照组相比,糖尿病患者的 E-选择素的上调趋势减弱,但血浆浓度往往更高。

结论

2 型糖尿病患者体内 TNF 和 IL-1ra 血浆水平的增加减弱,以及 LPS 诱导的 VCAM-1 和 ICAM-1 的上调减弱。这一发现可能为糖尿病患者在感染性疾病期间出现不良结局提供了一种机制解释。

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