Pro-Inflammatory Cytokines in Patients With Chronic Phase-Chronic Myeloid Leukaemia Treated With Imatinib: Any Role in the Monitoring of Treatment Response?
Kehinde A Taiwo, Ibrahim O Ahmed, Muritala A Asafa, Olusola J Olarewaju, Oludolapo A Omoyiola, Olatokunbo O Oguns, Temilola O Owojuyigbe, Rahman A Bolarinwa
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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, (t = 8.720 P ⩽ .0001), (8.45 ± 2.88 vs 2.86 ± 1.08 mg/l; t = 6.729 P ⩽ .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; t = -3.851 P = .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, (t = 8.055 P ⩽ .0001) and CRP (8.45 ± 2.88 mg/l vs 4.24 ± 1.57; t = 4.305 P = .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.
背景：癌症通过抑制或促进炎症细胞因子的产生，从而影响免疫系统，从而引起炎症细胞因子水平的变化。血清细胞因子水平的测量可能对评估这些免疫变化和评估癌症状态有用。目的：探讨甲磺酸伊马替尼（glivec®）对慢性髓性白血病（CP-CML）患者血清白细胞介素（IL-6、IL-10）和c反应蛋白（CRP）水平的影响。设计：这项前瞻性队列研究包括26名伊马替尼naïve无其他合并症的CP-CML患者和26名年龄和性别匹配的健康对照。方法：采用ELISA法测定患者和对照组招募时血清白细胞介素（il - 6、10）和CRP水平，并在伊马替尼治疗3个月时对CML患者进行重复检测。结果：招募期CP-CML患者血清IL-6和CRP平均水平（439.83±167.52 vs 39.62±10.11 pg/ml）显著高于对照组（t = 8.720 P≤0.0001），(8.45±2.88 vs 2.86±1.08 mg/l；t = 6.729 P≤0.0001)。对照组IL-10均值（36.63±12.43）明显高于对照组（22.88±4.76 vs 36.63±12.43 pg/ml）；t = -3.851 P = .003)。有趣的是，血清IL-6（439.83±167.52 vs 46.85±14.48 pg/ml, t = 8.055 P≤0.0001）和CRP（8.45±2.88 mg/l vs 4.24±1.57）水平显著下降；t = 4.305 P = 0.0001)，在接受伊马替尼治疗3个月的CML受试者中。在伊马替尼治疗3个月后，只有IL-10在CML患者中没有显著下降。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，naïve CML治疗与促炎细胞因子（IL-6和CRP）的显著升高相关，伊马替尼治疗导致这些标志物的血清水平显著下降，提示IL-6和CRP可作为CML治疗监测的辅助手段。
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