Serum cytokine profiles in infants with infantile hemangiomas on oral propranolol treatment: VEGF and bFGF, potential biomarkers predicting clinical outcomes
Serum cytokine profiles in infants with infantile hemangiomas on oral propranolol treatment: VEGF and bFGF, potential biomarkers predicting clinical outcomes
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DOI：
10.1038/s41390-020-0862-1
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发表时间：
2020-11-01
影响因子：
3.6
通讯作者：
Choi, Young Bae
中科院分区：
文献类型：
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作者：
Park, Meerim;Jung, Hye Lim;Choi, Young Bae
背景口服普萘洛尔已成为婴儿血管瘤（IH）的一线治疗。本研究的重点是确定细胞因子相关的生物学IH和早期回归指标的IH普萘洛尔治疗后。方法入选的患者年龄必须小于1岁，并且具有最大直径>= 2 cm的IH。患者计划接受1年普萘洛尔治疗。在治疗后0、1和/或12个月，使用Multiplex Luminex测定法分析参与血管生成、血管发生和/或慢性炎症的血清细胞因子。结果49例可评价的患者中，33例完成了1年的治疗，其中16例对普萘洛尔反应良好，12例反应良好。与治疗前值相比，治疗1年后观察到血清MMP-2、bFGF、VEGF-α和MCP-1水平显著降低。病变的最大直径与治疗前血清VEGF-α、bFGF和MMP-9显著相关。bFGF和VEGF水平较高的患者在1年时对普萘洛尔的反应更好。结论MMP-2、VEGF-α、bFGF和MCP-1可能参与了IH的生物学过程，其下调可能与IH的退化过程有关。治疗前bFGF和VEGF可能是预测普萘洛尔反应的新生物标志物。影响我们发现MMP-2、bFGF、VEGF和MCP-1浓度的降低与血管瘤的消退相关，这表明普萘洛尔治疗增殖性血管瘤的机制之一可能涉及这些细胞因子的下调。bFGF和VEGF水平较高的患者在1年时对普萘洛尔的反应更好。重要的是，血清bFGF高于37.07 pg/mL可预测对普萘洛尔的良好反应。因此，沿着患者的年龄和病变的大小和视觉特征，bFGF水平可以帮助确定普萘洛尔用于治疗IH的可行性。我们的研究代表了IH的广泛血清分析，报告了与普萘洛尔治疗的IH消退明显相关的指标和分子。作者认为，除了临床随访外，监测IH患者的血清细胞因子（包括MMP-2、bFGF、VEGF和MCP-1）对于确定何时开始和结束普萘洛尔治疗也很重要。
Background Oral propranolol has become first-line treatment for infantile hemangiomas (IHs). This study focused on identifying cytokines related to the biology of IH and early regression indicators of IH after propranolol treatment. Methods For inclusion, the patients had to be aged less than 1 year and have an IH with a largest diameter >= 2 cm. Patients were scheduled to receive 1 year of propranolol treatment. Serum cytokines involved in angiogenesis, vasculogenesis, and/or chronic inflammation were analyzed at 0, 1, and/or 12 months after treatment using Multiplex Luminex assays. Results Among the 49 evaluable patients, 33 completed the 1-year treatment: 16 showed excellent response and 12 had good response to propranolol. Significant decreases in serum MMP-2, bFGF, VEGF-alpha, and MCP-1 levels were observed after 1 year of treatment compared to pretreatment values. The maximal diameters of the lesions significantly correlated with pretreatment serum VEGF-alpha, bFGF, and MMP-9. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. Conclusion MMP-2, VEGF-alpha, bFGF, and MCP-1 may involve in the biology of IH and their downregulation may be associated with involution processes of IH. Pretreatment bFGF and VEGF could be novel biomarkers for predicting response to propranolol. ImpactWe found that decreases in the concentrations of MMP-2, bFGF, VEGF, and MCP-1 were associated with regression of the hemangioma, which indicates that one of the mechanisms of propranolol in the treatment of proliferative hemangiomas may involve downregulation of those cytokines. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. Importantly, serum bFGF higher than 37.07 pg/mL may predict an excellent response to propranolol. Therefore, along with the patient's age and the size and visual characteristics of the lesion, bFGF levels could help determine the viability of propranolol use in the treatment of IHs. Our study represented extensive serum profiling in IH, reporting the indicators and molecules clearly related to IH regression with propranolol treatment. The authors believe that monitoring serum cytokines, including MMP-2, bFGF, VEGF, and MCP-1, in IH patients could be important, in addition to clinical follow-up, for determining when to start and end propranolol treatment.