Pastori Silvia, Virzì Grazia Maria, Brocca Alessandra, de Cal Massimo, Clementi Anna, Vescovo Giorgio, Ronco Claudio
Department of Nephrology, Dialysis and Transplantation, Vicenza, Italy ; IRRIV-International Renal Resarch Institute Vicenza, Vicenza, Italy ; Department of Information Engineering, University of Padua, Italy.
Department of Nephrology, Dialysis and Transplantation, Vicenza, Italy ; IRRIV-International Renal Resarch Institute Vicenza, Vicenza, Italy.
Cardiorenal Med. 2015 Apr;5(2):105-15. doi: 10.1159/000371898. Epub 2015 Feb 11.
In this study, we examined the possible immune-mediated mechanisms in cardiorenal syndrome (CRS) type 1 pathogenesis. We enrolled 40 patients with acute heart failure (AHF), 11 patients with CRS type 1 and 15 controls. Plasma from the different groups was incubated with monocytes; subsequently, cell apoptosis was evaluated by DNA fragmentation, caspase activity and cytofluorometric assay. Cytokine quantification in plasma and supernatant was performed by ELISA. Monocytes treated with CRS type 1 plasma showed significantly higher apoptosis compared with those treated with AHF and the controls (p < 0.05). Caspase-3 (CRS type 1: 2.20 ng/ml, IQR 2.06-2.33; AHF: 1.48 ng/ml, IQR 1.31-1.56; controls: 0.71 ng/ml, IQR 0.67-0.81) and caspase-8 levels (CRS type 1: 1.49 ng/ml, IQR 1.42-1.57; AHF: 0.94 ng/ml, IQR 0.84-0.98; controls: 0.56 ng/ml, IQR 0.51-0.58) in cells incubated with plasma from these patients demonstrated a significantly higher concentration. We observed a strong upregulation of plasma IL-6 and IL-18 in CRS type 1 compared with AHF and the controls (p < 0.05). Interestingly, we observed a similar concentration of TNF-α in CRS type 1 and AHF. In CRS type 1 patients, IL-6 (52.13 ng/ml, IQR 47.29-66.83) and IL-18 levels (197.75 ng/ml, IQR 120.80-265.49) in supernatant were significantly higher than in AHF patients (IL-6: 28.79 ng/ml, IQR 19.90-36.10; IL-18: 21.98 ng/ml, IQR 15.98-29.85) and controls (IL-6: 5.02 ng/ml, IQR 4.56-6.44; IL-18: 7.91 ng/ml, IQR 5.57-10.62). These findings suggest the presence of a defective regulation of monocyte apoptosis in CRS type 1 patients and the involvement of an immune-mediated mechanism in the pathophysiology of this syndrome.
在本研究中，我们探讨了1型心肾综合征（CRS）发病机制中可能的免疫介导机制。我们纳入了40例急性心力衰竭（AHF）患者、11例1型CRS患者和15例对照。将不同组的血浆与单核细胞一起孵育；随后，通过DNA片段化、半胱天冬酶活性和细胞荧光分析评估细胞凋亡。采用酶联免疫吸附测定法（ELISA）对血浆和上清液中的细胞因子进行定量分析。与用AHF血浆和对照血浆处理的单核细胞相比，用1型CRS血浆处理的单核细胞显示出明显更高的凋亡率（p<0.05）。在与这些患者血浆一起孵育的细胞中，半胱天冬酶-3（1型CRS：2.20 ng/ml，四分位间距2.06 - 2.33；AHF：1.48 ng/ml，四分位间距1.31 - 1.56；对照：0.71 ng/ml，四分位间距0.67 - 0.81）和半胱天冬酶-8水平（1型CRS：1.49 ng/ml，四分位间距1.42 - 1.57；AHF：0.94 ng/ml，四分位间距0.84 - 0.98；对照：0.56 ng/ml，四分位间距0.51 - 0.58）的浓度明显更高。我们观察到，与AHF和对照相比，1型CRS患者血浆中白细胞介素-6（IL-6）和白细胞介素-18明显上调（p < 0.05）。有趣的是，我们观察到1型CRS患者和AHF患者的肿瘤坏死因子-α（TNF-α）浓度相似。在1型CRS患者中，上清液中的IL-6（52.13 ng/ml，四分位间距47.29 - 66.83）和IL-18水平（197.75 ng/ml，四分位间距120.80 - 265.49）明显高于AHF患者（IL-6：28.79 ng/ml，四分位间距19.90 - 36.10；IL-18：21.98 ng/ml，四分位间距15.98 - 29.85）和对照（IL-6：5.02 ng/ml，四分位间距4.56 - 6.44；IL-18：7.91 ng/ml，四分位间距5.57 - 10.62）。这些发现表明，1型CRS患者存在单核细胞凋亡调节缺陷，且免疫介导机制参与了该综合征的病理生理学过程。
