Kjaergaard A G, Nielsen J S, Tønnesen E, Krog J
Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus C, Denmark; Department of Anaesthesiology and Intensive Care, Randers Regional Hospital, Randers, Denmark.
Scand J Immunol. 2015 Apr;81(4):249-58. doi: 10.1111/sji.12272.
Sepsis is characterized by activation of both the innate and adaptive immune systems as a response to infection. During sepsis, the expression of surface receptors expressed on immune competent cells, such as NKG2D and NKp30 on NK cells and TLR4 and CD14 on monocytes, is partly regulated by pro- and anti-inflammatory mediators. In this observational study, we aimed to explore whether the expression of these receptors could be used as diagnostic and/or prognostic biomarkers in sepsis. Patients with severe sepsis or septic shock (n = 21) were compared with critically ill non-septic patients (n = 15). Healthy volunteers (n = 15) served as controls. To elucidate variations over time, all patients were followed for 4 days. Cell surface expression of NKG2D, NKp30, TLR4 and CD14 and serum levels of IL-1β, IL-6, IFN-γ, TNF-α, IL-4 and IL-10 was estimated by flow cytometry. We found that NK cell expression of NKG2D and monocyte expression of CD14 were lower in the septic patients compared with the non-septic patients, both at ICU admission and during the observation period (P < 0.01 for all comparisons). Both at ICU admission, and during the observation period, levels of IL-6 and IL-10 were higher in the septic patients compared with the non-septic patients (P < 0.001 for all comparisons).
As both NKG2D and CD14 levels appear to distinguish between septic and non-septic patients, both NKG2D and CD14 may be considered potential diagnostic biomarkers of severe sepsis and septic shock.
脓毒症的特征是先天性和适应性免疫系统作为对感染的反应而被激活。在脓毒症期间,免疫活性细胞表面表达的受体,如自然杀伤细胞(NK细胞)上的NKG2D和NKp30,以及单核细胞上的Toll样受体4(TLR4)和CD14,其表达部分受促炎和抗炎介质调节。在这项观察性研究中,我们旨在探讨这些受体的表达是否可作为脓毒症的诊断和/或预后生物标志物。将严重脓毒症或脓毒性休克患者(n = 21)与危重症非脓毒症患者(n = 15)进行比较。健康志愿者(n = 15)作为对照。为了阐明随时间的变化,对所有患者进行了4天的随访。通过流式细胞术估计NKG2D、NKp30、TLR4和CD14的细胞表面表达以及白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、干扰素-γ(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-4(IL-4)和白细胞介素-10(IL-10)的血清水平。我们发现,与非脓毒症患者相比,脓毒症患者在重症监护病房(ICU)入院时和观察期间,NK细胞的NKG2D表达和单核细胞的CD14表达均较低(所有比较P < 0.01)。在ICU入院时和观察期间,脓毒症患者的IL-6和IL-10水平均高于非脓毒症患者(所有比较P < 0.001)。
由于NKG2D和CD14水平似乎可区分脓毒症和非脓毒症患者,因此NKG2D和CD14均可被视为严重脓毒症和脓毒性休克的潜在诊断生物标志物。