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伊马替尼治疗慢性期慢性髓性白血病患者中的促炎细胞因子:在治疗反应监测中起作用吗?

Pro-Inflammatory Cytokines in Patients With Chronic Phase-Chronic Myeloid Leukaemia Treated With Imatinib: Any Role in the Monitoring of Treatment Response?

作者信息

Taiwo Kehinde A, Ahmed Ibrahim O, Asafa Muritala A, Olarewaju Olusola J, Omoyiola Oludolapo A, Oguns Olatokunbo O, Owojuyigbe Temilola O, Bolarinwa Rahman A

机构信息

Department of Haematology and Blood Transfusion, Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria.

Department of Physiological Sciences, Faculty of Basic Medical Sciences, College of Health Sciences, Obafemi Awolowo University, Ile-Ife, Nigeria.

出版信息

Biomark Insights. 2025 Jun 30;20:11772719251351687. doi: 10.1177/11772719251351687. eCollection 2025.

DOI:10.1177/11772719251351687
PMID:40606776
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12214318/
Abstract

BACKGROUND

Cancers cause changes in the levels of inflammatory cytokines by inhibiting or promoting their production thus affecting the immune system. The measurement of serum levels of cytokines may be useful in assessing these immunological changes and invariably assessing cancer status.

OBJECTIVES

To investigate the effect of imatinib mesylate (glivec) on the serum levels of interleukins (IL-6 and IL-10), and C-reactive protein (CRP) in patients with chronic phase chronic myeloid leukaemia (CP-CML).

DESIGN

This prospective cohort study included 26 imatinib naïve CP-CML patients with no other co-morbidities and 26 age and sex-matched healthy controls.

METHOD

Serum levels of interleukins (IL6 and 10) and CRP were determined using the ELISA method at recruitment for both patients and controls and repeated for the CML patients at 3 months into imatinib therapy.

RESULTS

The mean serum levels of IL-6 and CRP were significantly higher in CP-CML than in the controls at recruitment 439.83 ± 167.52 versus 39.62 ± 10.11 pg/ml, ( = 8.720  ⩽ .0001), (8.45 ± 2.88 vs 2.86 ± 1.08 mg/l;  = 6.729  ⩽ .0001) respectively. In contrast, the mean of the IL-10 in the controls (36.63 ± 12.43) was noticed to be significantly higher than the patients (22.88 ± 4.76 vs 36.63 ± 12.43 pg/ml;  = -3.851  = .003). Interestingly, there was a significant drop in the serum levels of IL-6 (439.83 ± 167.52 vs 46.85 ± 14.48 pg/ml, ( = 8.055  ⩽ .0001) and CRP (8.45 ± 2.88 mg/l vs 4.24 ± 1.57;  = 4.305  = .0001) in the CML subjects 3 months into imatinib therapy. Only IL-10 had a non-significant drop in the CML subjects after 3 months of imatinib therapy. Method validation of these biomarkers was done using the Receiver operating characteristic (ROC) curve which revealed an area under the curve (AUC) of 1.000 for both IL-6 and CRP and 0.152 for IL-10.

CONCLUSION

The study has concluded that treatment naïve CML is associated with a significant elevation of pro-inflammatory cytokines (IL-6 and CRP) and treatment with imatinib led to a significant decline in the serum levels of these markers suggesting that IL-6 and CRP could be useful as adjunct in the monitoring of CML treatment.

摘要

背景

癌症通过抑制或促进炎症细胞因子的产生来改变其水平,从而影响免疫系统。检测细胞因子的血清水平可能有助于评估这些免疫变化,并始终如一地评估癌症状态。

目的

研究甲磺酸伊马替尼(格列卫)对慢性期慢性髓性白血病(CP-CML)患者血清白细胞介素(IL-6和IL-10)及C反应蛋白(CRP)水平的影响。

设计

这项前瞻性队列研究纳入了26例初治的无其他合并症的CP-CML患者以及26例年龄和性别匹配的健康对照者。

方法

采用酶联免疫吸附测定(ELISA)法在招募患者和对照者时测定其血清白细胞介素(IL-6和IL-10)及CRP水平,并在伊马替尼治疗3个月时对CML患者重复测定。

结果

招募时,CP-CML患者的IL-6和CRP平均血清水平显著高于对照组,分别为439.83±167.52 pg/ml 对39.62±10.11 pg/ml,(t = 8.720,P⩽.0001),(8.45±2.88 mg/l对2.86±1.08 mg/l;t = 6.729,P⩽.0001)。相比之下,对照组的IL-10平均值(36.63±12.43)显著高于患者(22.88±4.76对36.63±12.43 pg/ml;t = -3.851,P =.003)。有趣的是,伊马替尼治疗3个月时,CML患者的血清IL-6水平(439.83±167.52对46.85±14.48 pg/ml,(t = 8.055,P⩽.0001)和CRP水平(8.45±2.88 mg/l对4.24±1.57;t = 4.305,P =.0001)显著下降。伊马替尼治疗3个月后,CML患者中只有IL-10有不显著的下降。使用受试者工作特征(ROC)曲线对这些生物标志物进行方法验证,结果显示IL-6和CRP的曲线下面积(AUC)均为1.000,IL-10的AUC为0.152。

结论

该研究得出结论,初治的CML与促炎细胞因子(IL-6和CRP)显著升高有关,伊马替尼治疗导致这些标志物的血清水平显著下降,这表明IL-6和CRP可作为监测CML治疗的辅助指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883e/12214318/fd754c42a8e1/10.1177_11772719251351687-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883e/12214318/9a506592d29e/10.1177_11772719251351687-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883e/12214318/fd754c42a8e1/10.1177_11772719251351687-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883e/12214318/9a506592d29e/10.1177_11772719251351687-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/883e/12214318/fd754c42a8e1/10.1177_11772719251351687-fig2.jpg

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