Versace Antonio Giovanni, Bitto Alessandra, Ioppolo Carmelo, Aragona Caterina Oriana, La Rosa Daniela, Roberts William Neal, D'Angelo Tommaso, Cinquegrani Antonella, Cirmi Santa, Irrera Natasha, Navarra Michele, Corrao Salvatore, Gangemi Sebastiano, Bagnato Gianluca
Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
Department of Medicine, University of Kentucky, Lexington, KY, United States.
Front Med (Lausanne). 2022 Feb 17;9:825567. doi: 10.3389/fmed.2022.825567. eCollection 2022.
Systemic sclerosis (SSc) mortality is extremely variable in its internal organ involvement. Pulmonary fibrosis occurs in up to 30% of the cases. Animal models provide evidence that IL-33 is able to induce both cutaneous and pulmonary fibrosis via increased IL-13 and in SSc patients the levels of IL-33 correlate with skin fibrosis. Our aim was to test whether both IL-33 and IL-13 are higher in patients with diffuse SSc and interstitial lung disease (SSc-ILD) compared to SSc patients without ILD and healthy controls.
Serum levels of IL-13 and IL-33 were measured in 30 SSc patients with diffuse disease and 30 healthy controls by enzyme-linked immunosorbent assay. The extent of pulmonary fibrosis was assessed according to HRCT Warrick score. Pulmonary function tests included lung diffusion capacity for carbon monoxide, forced vital capacity and total lung capacity.
Both IL-13 and IL-33 levels were increased in SSc patients compared to controls and significantly associated each other. DLco, FVC and TLC scores were inversely associated with IL-33 and IL-13 levels. Both IL-33 and IL-13 levels were significantly associated with the Warrick severity score and higher in the group of SSc patients with reduced pulmonary function compared to SSc patients with normal pulmonary function tests.
The IL-13/IL-33 axis needs to be further explored in longitudinal studies of SSc-ILD patients to assess its validity as a biomarker and future treatment target, as does downstream mediator ST2.
系统性硬化症(SSc)患者的死亡率在其内脏器官受累方面差异极大。高达30%的病例会出现肺纤维化。动物模型表明,白细胞介素-33(IL-33)能够通过增加白细胞介素-13(IL-13)来诱导皮肤和肺纤维化,且在SSc患者中,IL-33水平与皮肤纤维化相关。我们的目的是检测与无ILD的SSc患者及健康对照相比,弥漫性SSc合并间质性肺病(SSc-ILD)患者的IL-33和IL-13水平是否更高。
采用酶联免疫吸附测定法测量30例弥漫性疾病的SSc患者和30例健康对照的血清IL-13和IL-33水平。根据HRCT沃里克评分评估肺纤维化程度。肺功能测试包括一氧化碳肺弥散量、用力肺活量和肺总量。
与对照组相比,SSc患者的IL-13和IL-33水平均升高,且二者显著相关。一氧化碳肺弥散量、用力肺活量和肺总量评分与IL-33和IL-13水平呈负相关。IL-33和IL-13水平均与沃里克严重程度评分显著相关,与肺功能测试正常的SSc患者相比,肺功能降低的SSc患者组中的这两种水平更高。
在SSc-ILD患者的纵向研究中,需要进一步探索IL-13/IL-33轴,以评估其作为生物标志物和未来治疗靶点的有效性,下游介质ST2也是如此。