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探讨结核病中的细胞因子动态:来自为期三周抗结核干预的患者和对照的比较分析。

Exploring cytokine dynamics in tuberculosis: A comparative analysis of patients and controls with insights from three-week antituberculosis intervention.

机构信息

Jessenius Faculty of Medicine in Martin, Biomedical Centre Martin, Comenius University Bratislava, Martin, Slovak Republic.

Jessenius Faculty of Medicine in Martin, Department of Pharmacology, Comenius University Bratislava, Martin, Slovak Republic.

出版信息

PLoS One. 2024 Aug 29;19(8):e0305158. doi: 10.1371/journal.pone.0305158. eCollection 2024.

DOI:10.1371/journal.pone.0305158
PMID:39208230
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11361567/
Abstract

Despite developing new diagnostics, drugs, and vaccines, treating tuberculosis (TB) remains challenging. Monitoring inflammatory markers can contribute to more precise diagnostics of TB, identifying its active and latent forms, or monitoring its treatment success. We assessed alterations in plasma levels of 48 cytokines in 20 patients (17 males) with active pulmonary TB compared to age-matched healthy controls (n = 18). Blood samples were collected from individuals hospitalised with TB prior to commencing antibiotic therapy, after the first week, and following the third week. The majority of patients received treatment with a combination of four first-line antituberculosis drugs: rifampicin, isoniazid, ethambutol, and pyrazinamide. Plasmatic cytokine levels from patients three times and controls were analyzed using a Bio-Plex Pro Human Cytokine Screening Panel. The results showed significantly higher levels of 31 cytokines (p<0.05) than healthy controls. Three-week therapy duration showed significantly decreased levels of nine cytokines: interferon alpha-2 (IFN-α2), interleukin (IL) 1 alpha (IL-1α), IL-1 receptor antagonist (IL-1ra), IL-6, IL-10, IL-12 p40, IL-17, leukemia inhibitory factor (LIF), and tumor necrosis factor alpha (TNF-α). Out of these, only levels of IL-1α and IL-6 remained significantly elevated compared to controls. Moreover, we have found a negative correlation of 18 cytokine levels with BMI of the patients but no correlation with age. Our results showed a clinical potential for monitoring the levels of specific inflammatory markers after a short treatment duration. The reduction in cytokine levels throughout the course of therapy could indicate treatment success but should be confirmed in studies with more individuals involved and a longer observation period.

摘要

尽管开发了新的诊断方法、药物和疫苗,但是治疗结核病(TB)仍然具有挑战性。监测炎症标志物有助于更精确地诊断 TB,识别其活动期和潜伏性形式,或监测其治疗效果。我们评估了 20 例活动性肺结核患者(17 名男性)与年龄匹配的健康对照组(n = 18)的血浆中 48 种细胞因子水平的变化。在开始抗生素治疗之前、第一周后和第三周后,从住院的 TB 患者中采集血液样本。大多数患者接受了包含四种一线抗结核药物的联合治疗:利福平、异烟肼、乙胺丁醇和吡嗪酰胺。使用 Bio-Plex Pro 人类细胞因子筛选试剂盒分析患者三次和对照组的血浆细胞因子水平。结果显示,患者的 31 种细胞因子水平显著高于健康对照组(p<0.05)。三周的治疗时间显示,九种细胞因子的水平显著降低:干扰素-α2(IFN-α2)、白细胞介素(IL)1α(IL-1α)、IL-1 受体拮抗剂(IL-1ra)、IL-6、IL-10、IL-12 p40、IL-17、白血病抑制因子(LIF)和肿瘤坏死因子-α(TNF-α)。其中,只有 IL-1α 和 IL-6 的水平仍显著高于对照组。此外,我们发现 18 种细胞因子的水平与患者的 BMI 呈负相关,但与年龄无关。我们的结果表明,在短时间的治疗后监测特定炎症标志物的水平具有临床潜力。治疗过程中细胞因子水平的降低可能表明治疗成功,但应在涉及更多患者和更长观察期的研究中得到证实。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa32/11361567/a08a870be4e6/pone.0305158.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa32/11361567/39ac7c7fbdbf/pone.0305158.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa32/11361567/575bc16ddbef/pone.0305158.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa32/11361567/e3817a22ef67/pone.0305158.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa32/11361567/a08a870be4e6/pone.0305158.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa32/11361567/39ac7c7fbdbf/pone.0305158.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa32/11361567/575bc16ddbef/pone.0305158.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa32/11361567/e3817a22ef67/pone.0305158.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa32/11361567/a08a870be4e6/pone.0305158.g004.jpg

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