Department of Digestive Disease, University Campus Bio-Medico, Via Alvaro del Portillo, Rome, Italy.
Neurogastroenterol Motil. 2012 Oct;24(10):943-e463. doi: 10.1111/j.1365-2982.2012.01963.x. Epub 2012 Jun 26.
A distinction between symptomatic non-erosive reflux disease (NERD) and erosive esophagitis (EE) patients is supported by the presence of inflammatory response in the mucosa of EE patients, leading to a damage of mucosal integrity. To explore the underlying mechanism of this difference, we assessed inflammatory mediators in mucosal biopsies from EE and NERD patients and compared them with controls.
Nineteen NERD patients, 15 EE patients, and 16 healthy subjects underwent endoscopy after a 3-week washout from PPI or H(2) antagonists. Biopsies obtained from the distal esophagus were examined by quantitative real-time polymerase chain reaction (qPCR) and multiplex enzyme-linked immunosorbent assay for selected chemokines and lyso-PAF acetyltransferase (LysoPAF-AT), the enzyme responsible for production of platelet-activating factor (PAF).
Expression of LysoPAF-AT and multiple chemokines was significantly increased in mucosal biopsies derived from EE patients, when compared with NERD patients and healthy controls. Upregulated chemokines included interleukin 8, eotaxin-1, -2, and -3, macrophage inflammatory protein-1α (MIP-1α), and monocyte chemoattractant protein-1 (MCP-1). LysoPAF-AT and the chemokine profile in NERD patients were comparable with healthy controls.
CONCLUSIONS & INFERENCES: Levels of selected cytokines and Lyso-PAF AT were significantly higher in the esophageal mucosa of EE patients compared with NERD and control patients. This difference may explain the distinct inflammatory response occurring in EE patients' mucosa. In contrast, as no significant differences existed between the levels of all mediators in NERD and control subjects, an inflammatory response does not appear to play a major role in the pathogenesis of the abnormalities found in NERD patients.
EE 患者的黏膜存在炎症反应,导致黏膜完整性受损,这支持将有症状的非侵蚀性反流病(NERD)和侵蚀性食管炎(EE)患者区分开来。为了探究这种差异的潜在机制,我们评估了 EE 和 NERD 患者的黏膜活检标本中的炎症介质,并与对照组进行了比较。
19 名 NERD 患者、15 名 EE 患者和 16 名健康受试者在停用质子泵抑制剂或 H2 受体拮抗剂 3 周后进行了内镜检查。通过定量实时聚合酶链反应(qPCR)和多重酶联免疫吸附试验,对取自远端食管的活检标本进行了分析,检测了选定趋化因子和溶血小板激活因子(LysoPAF)乙酰转移酶(LysoPAF-AT)的表达,后者是产生血小板激活因子(PAF)的酶。
与 NERD 患者和健康对照组相比,EE 患者的黏膜活检标本中 LysoPAF-AT 和多种趋化因子的表达显著增加。上调的趋化因子包括白细胞介素 8、嗜酸性粒细胞趋化因子 1、2 和 3、巨噬细胞炎性蛋白 1α(MIP-1α)和单核细胞趋化蛋白 1(MCP-1)。NERD 患者的 LysoPAF-AT 和趋化因子谱与健康对照组相似。
与 NERD 和对照组患者相比,EE 患者食管黏膜中选定细胞因子和 LysoPAF AT 的水平显著升高。这种差异可能解释了 EE 患者黏膜中发生的不同炎症反应。相比之下,由于 NERD 和对照组患者的所有介质水平均无显著差异,因此炎症反应似乎不是 NERD 患者异常发生的主要原因。