Tyler Ryan E, Vizioli Carlotta, Barb Jennifer J, Farokhnia Mehdi, Leggio Lorenzo
Clinical Psychoneuroendocrinology and Neuropsychopharmacology (CPN) Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse Intramural Research Program and National Institute on Alcohol Abuse and Alcoholism Division of Intramural Clinical and Biological Research, National Institutes of Health, Baltimore, Maryland, USA.
National Institute of General Medical Sciences, Bethesda, Maryland, USA.
Addict Biol. 2025 May;30(5):e70039. doi: 10.1111/adb.70039.
Alcohol use disorder (AUD) is associated with changes in endocrine and immune system function. This study is a secondary analysis aimed at investigating changes in circulating immune and endocrine biomarkers in blood samples from three groups: (1) healthy controls (HC, N = 12), (2) AUD-currently drinking, nontreatment seeking (CD, N = 9), and (3) AUD-abstinent, treatment-seeking (AB, N = 10; abstinent for at least 6 weeks). We hypothesized that both immune and endocrine biomarker concentrations would be different in AUD groups compared to healthy controls. Immune biomarkers included IL-8, IL-18, CCL2, TNF-α, IL-1RA, IL-6, and IL-10. Endocrine biomarkers included brain-derived neurotrophic factor (BDNF), glucagon-like peptide 1 (GLP-1), ghrelin, gastric inhibitory peptide (GIP), growth hormone, leptin, and insulin. Biomarker concentrations were compared between the three groups while controlling for age and sex, and associations between biomarker concentrations and behavioral measures were explored. IL-8 concentrations were elevated in AB compared to CD and HC (F(2,29) = 6.33, p = 0.006, ƞ = 0.318). BDNF concentrations were lower in AB compared to HC (F(2,30) = 4.34, p = 0.02, ƞ = 0.266). GLP-1 concentrations were higher in AB compared to HC (F(2,25) = 4.22, p = 0.03, ƞ = 0.287). Exploratory analyses in combined groups showed that measures of past drinking, AUD severity, and anxiety/depression positively correlated with IL-18 and TNF-α and negatively correlated with BDNF. These results demonstrate that circulating concentrations of both immune and endocrine proteins are altered in abstinent individuals with a history of severe AUD (AB group) compared to healthy controls. In contrast, no group differences were observed for any biomarker between the nontreatment seeking, currently drinking people with AUD and the HC group. Our findings highlight the importance of accounting for AUD severity, comorbidities, and treatment-seeking status, especially when studying alcohol-related biomarkers.
酒精使用障碍（AUD）与内分泌和免疫系统功能的变化有关。本研究是一项二次分析，旨在调查三组血液样本中循环免疫和内分泌生物标志物的变化：（1）健康对照组（HC，N = 12），（2）AUD-当前饮酒、未寻求治疗组（CD，N = 9），以及（3）AUD-戒酒、寻求治疗组（AB，N = 10；戒酒至少6周）。我们假设，与健康对照组相比，AUD组的免疫和内分泌生物标志物浓度均会有所不同。免疫生物标志物包括白细胞介素-8（IL-8）、白细胞介素-18（IL-18）、趋化因子配体2（CCL2）、肿瘤坏死因子-α（TNF-α）、白细胞介素-1受体拮抗剂（IL-1RA）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）。内分泌生物标志物包括脑源性神经营养因子（BDNF）、胰高血糖素样肽1（GLP-1）、胃饥饿素、胃抑制肽（GIP）、生长激素、瘦素和胰岛素。在控制年龄和性别的同时，比较了三组之间的生物标志物浓度，并探讨了生物标志物浓度与行为指标之间的关联。与CD组和HC组相比，AB组的IL-8浓度升高（F(2,29) = 6.33，p = 0.006，ƞ = 0.318）。与HC组相比，AB组的BDNF浓度较低（F(2,30) = 4.34，p = 0.02，ƞ = 0.266）。与HC组相比，AB组的GLP-1浓度较高（F(2,25) = 4.22，p = 0.03，ƞ = 0.287）。联合组的探索性分析表明，既往饮酒量、AUD严重程度以及焦虑/抑郁与IL-18和TNF-α呈正相关，与BDNF呈负相关。这些结果表明，与健康对照组相比，有严重AUD病史的戒酒个体（AB组）的循环免疫和内分泌蛋白浓度均发生了改变。相比之下，未寻求治疗、当前饮酒的AUD患者与HC组之间，未观察到任何生物标志物的组间差异。我们的研究结果强调了考虑AUD严重程度、合并症和寻求治疗状态的重要性，尤其是在研究与酒精相关的生物标志物时。
