Vieira Érica Leandro Marciano, Pessoa Rocha Natalia, Macedo Bastos Fernando, da Silveira Kátia Daniela, Pereira Alamanda K, Araújo Oliveira Eduardo, Marques de Miranda Débora, Simões E Silva Ana Cristina
Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Universidade Federal de Minas Gerais (UFMG), Avenida Alfredo Balena, 190, 2° andar, sala 281, 30.130-100, Belo Horizonte, MG, Brazil.
Fetal Medicine Unit, Department of Gynecology and Obstetrics, UFMG, Belo Horizonte, MG, Brazil.
Pediatr Nephrol. 2017 Aug;32(8):1391-1400. doi: 10.1007/s00467-017-3614-7. Epub 2017 Feb 22.
The aim of this cross-sectional study was to investigate inflammatory biomarkers in urine samples of 24 fetuses with posterior urethral valve (PUV) collected at 22 ± 4 weeks of gestation and to compare the findings with measurements in urine samples of 22 male healthy preterm neonates at 23 ± 4 weeks (control group).
Inflammatory biomarkers in urine were measured using a cytometric bead array [interleukin (IL)-2, IL-4, IL-6, IL-10, interferon (IFN)-γ, soluable tumor necrosis factor receptor (TNFR) 1, sTNFR2, monocyte chemoattractant protein-1/chemokine ligand 2 (MCP-1/CCL2), eotaxin/CCL11 and interferon gamma-induced protein/10/C-X-C motif chemokine 10 (IP-10/CXCL10)] and ELISA assays [TNF, IL-8/CXCL8 and transforming growth factor-beta (TGF-β)]. The Mann-Whitney test was used to compare medians. Markers of glomerular (creatinine) and tubular [beta 2 (β)-microglobulin, uromodulin, osmolality] functions were correlated with inflammatory biomarkers (Spearman test).
An intense inflammatory profile was identified, with significantly increased concentrations of urinary IL-2, IL-4, IL-6, TNF, sTNFRI, sTNFRII, IFN-γ, MCP-1/CCL2, eotaxin/CCL11 and IL-8/CXCL8 in the PUV group compared to the controls. The same was observed for the anti-inflammatory cytokine IL-10 and for the fibrogenic mediator TGF-β. In the correlation analysis, β-microglobulin positively correlated with the presence of MCP-1/CCL2, sTNFRI and eotaxin/CCL11 and negatively correlated with the presence of creatinine.
This study shows that inflammatory molecules are already increased in fetuses with PUV at the mean gestational age of 22 weeks, suggesting a physiopathological role for inflammation just after the embryological formation of the urethral membrane.
本横断面研究的目的是调查在妊娠22±4周时收集的24例患有后尿道瓣膜（PUV）胎儿的尿液样本中的炎症生物标志物，并将结果与22例在23±4周的健康男性早产新生儿的尿液样本测量值进行比较（对照组）。
使用细胞计数珠阵列[白细胞介素（IL）-2、IL-4、IL-6、IL-10、干扰素（IFN）-γ、可溶性肿瘤坏死因子受体（TNFR）1、sTNFR2、单核细胞趋化蛋白-1/趋化因子配体2（MCP-1/CCL2）、嗜酸性粒细胞趋化因子/CCL11和干扰素γ诱导蛋白/10/C-X-C基序趋化因子10（IP-10/CXCL10）]和酶联免疫吸附测定（ELISA）[肿瘤坏死因子（TNF）、IL-8/CXCL8和转化生长因子-β（TGF-β）]测量尿液中的炎症生物标志物。采用曼-惠特尼检验比较中位数。肾小球（肌酐）和肾小管[β2（β）-微球蛋白、尿调节蛋白、渗透压]功能标志物与炎症生物标志物相关（斯皮尔曼检验）。
确定了一种强烈的炎症特征，与对照组相比，PUV组尿液中IL-2、IL-4、IL-6、TNF、sTNFRI、sTNFRII、IFN-γ、MCP-1/CCL2、嗜酸性粒细胞趋化因子/CCL11和IL-8/CXCL8的浓度显著增加。抗炎细胞因子IL-10和纤维化介质TGF-β也观察到同样情况。在相关性分析中，β-微球蛋白与MCP-1/CCL2、sTNFRI和嗜酸性粒细胞趋化因子/CCL11的存在呈正相关，与肌酐的存在呈负相关。
本研究表明，在平均妊娠年龄22周时，患有PUV的胎儿体内炎症分子已经增加，这表明在尿道膜胚胎形成后不久，炎症就具有生理病理作用。
