系统性硬化临床特征与病程以及血清白细胞介素8、血管内皮生长因子、基本成纤维细胞生长因子和干扰素阿尔法之间的关联。
Association between clinical features and course of systemic sclerosis and serum interleukin-8, vascular endothelial growth factor, basic fibroblast growth factor, and interferon alpha.
发表日期:2023 Aug 04
作者:
Joanna Kosałka-Węgiel, Sabina Lichołai, Sylwia Dziedzina, Mamert Milewski, Piotr Kuszmiersz, Anna Korona, Mariusz Korkosz, Jolanta Gąsior, Aleksandra Matyja-Bednarczyk, Helena Kwiatkowska, Andżelika Siwiec-Koźlik, Wojciech Sydor, Joanna Wilańska, Lech Zaręba, Weronika Pociej-Marciak, Jerzy Dropiński, Marek Sanak, Jacek Musiał, Stanisława Bazan-Socha
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
某些介质,例如可溶性生长因子和细胞因子等,与系统性硬化(SSc)的免疫病理生成相关。本研究旨在调查血清中血管内皮生长因子(VEGF)、白细胞介素-8(IL-8)、干扰素α(IFN-α)和碱性成纤维细胞生长因子(bFGF)的水平与SSc的临床表现和发病过程之间的关联。这项纵向观察研究纳入了43名SSc患者和24名健康受试者。在之前接受SSc治疗的患者中,测量了VEGF、IL-8、IFN-α和bFGF的血清浓度。在测量细胞因子的时间点上,回顾性分析了患者的病史以推断临床相关性,并在随访期间(中位数5年)评估了死亡或癌症的发生率。bFGF和IFN-α的浓度在SSc患者和对照组之间有差异(p < 0.01)。与此同时,器官受累和SSc表型对研究的细胞因子浓度没有影响,类似于系统性激素和/或免疫抑制剂的使用。然而,我们发现目前口服激素剂量与IL-8和bFGF的血清水平之间存在正相关。此外,血清中VEGF水平≥95.7 pg/mL和IFN-α水平≥3.6 pg/mL的患者更常需要环磷酰胺治疗,目前或过去需要(分别增多约3倍和4倍)。在随访期间,基线时明显升高的VEGF和IFN-α浓度与更高的癌症发生率(n = 4)相关,而升高的循环IL-8水平与死亡风险增加(n = 9)相关。与健康对照组相比,SSc组的血清bFGF和IFN-α浓度较高。接受环磷酰胺治疗或接受较高系统性激素剂量治疗的患者,即患有更严重的疾病类型,细胞因子水平升高。血清中升高的IFN-α和VEGF水平可能与癌症相关,而升高的循环IL-8水平可能与死亡风险增加相关。然而,需要进一步研究来验证我们的发现。
Certain mediators, such as soluble growth factors and cytokines, among others, are implicated in the immunopathogenesis of systemic sclerosis (SSc).This study aimed to examine the association between serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), interferon alpha (IFN-α), and basic fibroblast growth factor (bFGF) and the clinical presentation and course of SSc.This longitudinal, observational study included 43 patients with SSc and 24 healthy subjects. Serum concentrations of VEGF, IL-8, IFN-α, and bFGF were measured at baseline in patients previously treated for SSc. Medical history of patients was analyzed retrospectively at the time of cytokine measurement to infer clinical correlations, and during follow-up for a median of 5 years, assessing the incidence of death or cancer.The bFGF and IFN-α concentrations differed between SSc patients and controls (p < 0.01). In turn, organ involvement and SSc phenotypes did not impact studied cytokine concentrations, similar to systemic steroid and/or immunosuppressant use at enrollment. However, we have documented a positive correlation between the current oral steroid dose and serum levels of IL-8 and bFGF. Furthermore, patients with a VEGF level ≥95.7 pg/mL and IFN-α level ≥3.6 pg/mL required cyclophosphamide therapy more often, currently or in the past (approx. 3-fold and 4-fold, respectively). Substantially elevated VEGF and IFN-α concentrations at baseline were associated with higher cancer occurrence (n = 4) during follow-up, while elevated circulating IL-8 level was associated with an increased risk of death (n = 9).The SSc group was characterized by higher serum concentrations of bFGF and IFN-α compared to healthy controls. Patients treated with cyclophosphamide or receiving higher systemic steroid doses, thus suffering from a more severe disease type, had increased cytokine levels. Elevated circulating IFN-α and VEGF levels might be correlated with cancer, whereas raised IL-8 levels may be associated with an increased risk of death. However, further research is needed to verify our findings.