神经母细胞瘤患儿血清促炎和抗炎细胞因子浓度分析：一项初步研究。

Analysis of Pro-Inflammatory and Anti-Inflammatory Cytokine Serum Concentrations in Pediatric Patients with Neuroblastoma: A Preliminary Study.

作者信息

Moreno-Guerrero Silvia Selene, Ramírez-Pacheco Arturo, Rocha-Ramírez Luz María, Hernández-Pliego Gabriela, Reyes-López Alfonso, Sienra-Monge Juan José Luis, Juárez-Villegas Luis Enrique

机构信息

Departamento de Hemato-Oncología, Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col Doctores, Delegación Cuauhtémoc, Mexico City 06720, Mexico.

Unidad de Investigación en Enfermedades Infecciosas, Hospital Infantil de México Federico Gómez, Dr. Márquez No. 162, Col Doctores, Delegación Cuauhtémoc, Mexico City 06720, Mexico.

出版信息

Biomedicines. 2025 Jun 20;13(7):1517. doi: 10.3390/biomedicines13071517.

DOI:10.3390/biomedicines13071517

PMID:40722593

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12292616/

Abstract

Cytokines are effector molecules of the host immune response that have been associated with chronic inflammatory processes related to risk and a poor prognosis in cancer patients. However, the impact of these molecules on the genesis and prognosis of Neuroblastoma (NB) is uncertain. The aim of the study was to analyze serum concentrations of pro-inflammatory and anti-inflammatory cytokines in a cohort of pediatric patients with NB. We evaluated the serum levels of several cytokines with a pro-inflammatory profile (IL-8, MCP-1, IL-6, IL-1β, IFN-γ, TNF-α, IL-12 p40 and IL-12p70), and anti-inflammatory profile (IL-10 and TGF-β), in pediatric patients with NB using the ELISA method, compared to a healthy control group (non-oncology). Serum levels of pro-inflammatory cytokines IL-6, TNF-α, INF-γ, IL-12, IL-8 and MCP1 were significantly elevated in patients with NB compared to healthy pediatric controls. Only the anti-inflammatory cytokine IL-10 showed high levels in patients with NB in relation to the control group, unlike the synthesis of TGF-β, which had no differences between both groups. Likewise, significant positive correlations were found between the circulating levels of IL-6 with TNF-α (r = 0.667; ≤ 0.01), IL-6 with IL-8 (r = 0.641; ≤ 0.01), IL-8 with TNF-α (r = 0.637; ≤ 0.01) and IL-10 with INF-γ (r = 0.542; ≤ 0.01) in patients with NB. The simple logistic regression analysis revealed a significant association between low serum concentrations of IL-6 and a lower risk of presenting an unfavorable tumor histology ( = 0.048); in addition, low levels of IL-12p40 ( = 0.007), IFN-γ ( = 0.006) and MCP-1 ( = 0.029) were found to be associated with a lower risk of presenting NB in disseminated stages of the disease (INSS 3 and 4). Additionally, a higher risk of death was found in patients with high levels of IL-6 ( = 0.022) and IL-8 ( = 0.04). Taken together, the results demonstrate that the serum levels of pro-inflammatory cytokines such as IL-6, IL-8, IFN-γ, and TNF-α could be considered serum immunological indicators with a potential prognostic role in the pathogenesis of NB.

摘要

细胞因子是宿主免疫反应的效应分子，与癌症患者的风险及不良预后相关的慢性炎症过程有关。然而，这些分子对神经母细胞瘤（NB）发生及预后的影响尚不确定。本研究旨在分析一组患NB的儿科患者血清中促炎和抗炎细胞因子的浓度。我们采用酶联免疫吸附测定（ELISA）法，评估了一组患NB的儿科患者血清中几种具有促炎特征的细胞因子（白细胞介素-8（IL-8）、单核细胞趋化蛋白-1（MCP-1）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、白细胞介素-12 p40和白细胞介素-12p70）以及具有抗炎特征的细胞因子（白细胞介素-10（IL-10）和转化生长因子-β（TGF-β））的水平，并与健康对照组（非肿瘤患者）进行比较。与健康儿科对照组相比，患NB患者血清中促炎细胞因子IL-6、TNF-α、INF-γ、IL-12、IL-8和MCP1水平显著升高。与对照组相比，仅抗炎细胞因子IL-10在患NB患者中显示高水平，而TGF-β的合成在两组之间无差异。同样，在患NB患者中发现，IL-6与TNF-α的循环水平之间存在显著正相关（r = 0.667；P≤0.01），IL-6与IL-8之间（r = 0.641；P≤0.01），IL-8与TNF-α之间（r = 0.637；P≤0.01）以及IL-10与INF-γ之间（r = 0.542；P≤0.01）。简单逻辑回归分析显示，血清IL-6浓度低与肿瘤组织学不良风险较低之间存在显著关联（P = 0.048）；此外，发现低水平的IL-12p40（P = 0.007）、IFN-γ（P = 0.006）和MCP-1（P = 0.029）与疾病播散期（国际神经母细胞瘤分期系统（INSS）3期和4期）患NB的风险较低相关。此外，发现IL-6水平高（P = 0.022）和IL-8水平高（P = 0.04）的患者死亡风险较高。综上所述，结果表明，促炎细胞因子如IL-6、IL-8、IFN-γ和TNF-α的血清水平可被视为在NB发病机制中具有潜在预后作用的血清免疫学指标。