Department of Internal Medicine I, University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany.
Department of Cardiothoracic Surgery, University Hospital Jena, Am Klinikum 1, 07747 Jena, Germany.
Int J Mol Sci. 2024 Apr 3;25(7):3985. doi: 10.3390/ijms25073985.
Growing evidence suggests the crucial involvement of inflammation in the pathogenesis of pulmonary hypertension (PH). The current study analyzed the expression of interleukin (IL)-17a and IL-22 as potential biomarkers for PH in a preclinical rat model of PH as well as the serum levels in a PH patient collective. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in 10 Sprague Dawley rats (PH) and compared to 6 sham-treated controls (CON) as well as 10 monocrotalin-induced, macitentan-treated rats (PH_MAC). Lung and cardiac tissues were subjected to histological and immunohistochemical analysis for the ILs, and their serum levels were quantified using ELISA. Serum IL levels were also measured in a PH patient cohort. IL-22 expression was significantly increased in the lungs of the PH and PH_MAC groups ( = 0.002), whereas increased IL17a expression was demonstrated only in the lungs and RV of the PH ( < 0.05) but not the PH_MAC group ( = n.s.). The PH group showed elevated serum concentrations for IL-22 ( = 0.04) and IL-17a ( = 0.008). Compared to the PH group, the PH_MAC group demonstrated a decrease in IL-22 ( = 0.021) but not IL17a ( = n.s.). In the PH patient collective ( = 92), increased serum levels of IL-22 but not IL-17a could be shown ( < 0.0001). This elevation remained significant across the different etiological groups ( < 0.05). Correlation analysis revealed multiple significant relations between IL-22 and various clinical, laboratory, functional and hemodynamic parameters. IL-22 could serve as a promising inflammatory biomarker of PH with potential value for initial diagnosis, functional classification or even prognosis estimation. Its validation in larger patients' cohorts regarding outcome and survival data, as well as the probability of promising therapeutic target structures, remains the object of further studies.
越来越多的证据表明，炎症在肺动脉高压（PH）的发病机制中起着关键作用。本研究分析了白细胞介素（IL）-17a 和 IL-22 在 PH 临床前大鼠模型中的表达，以及 PH 患者群体中的血清水平。通过皮下注射（60mg/kg 体重）单环素来诱导 PH，在 10 只 Sprague Dawley 大鼠（PH 组）中诱导 PH，并与 6 只假手术对照（CON 组）以及 10 只单环素诱导、马西替坦治疗的大鼠（PH_MAC 组）进行比较。对肺和心脏组织进行 IL 的组织学和免疫组织化学分析，并使用 ELISA 定量其血清水平。还在 PH 患者队列中测量了血清 IL 水平。PH 和 PH_MAC 组肺组织中 IL-22 表达明显增加（ = 0.002），而 PH 组肺和 RV 中仅显示出增加的 IL17a 表达（ < 0.05），但 PH_MAC 组未显示（ = n.s.）。PH 组血清中 IL-22（ = 0.04）和 IL-17a（ = 0.008）浓度升高。与 PH 组相比，PH_MAC 组 IL-22 （ = 0.021）降低，但 IL17a （ = n.s.）未降低。在 PH 患者群体（ = 92）中，可显示出血清中 IL-22 但不是 IL-17a 水平升高（ < 0.0001）。这种升高在不同病因组中仍然具有统计学意义（ < 0.05）。相关性分析显示，IL-22 与各种临床、实验室、功能和血液动力学参数之间存在多种显著关系。IL-22 可能是 PH 的一种有前途的炎症生物标志物，具有潜在的初始诊断、功能分类甚至预后估计价值。在更大的患者队列中对其进行验证，以获得有关结局和生存数据，以及潜在的有前途的治疗靶标结构的可能性，仍然是进一步研究的目标。
