Necrotising enterocolitis (NEC) is an uncommon, but devastating intestinal inflammatory disease that predominantly affects preterm infants. NEC is sometimes dubbed the spectre of neonatal intensive care units, as its onset is insidiously non-specific, and once the disease manifests, the damage inflicted on the baby's intestine is already disastrous. Subsequent sepsis and multi-organ failure entail a mortality of up to 65%. Development of effective treatments for NEC has stagnated, largely because of our lack of understanding of NEC pathogenesis. It is clear, however, that NEC is driven by a profoundly dysregulated immune system. NEC is associated with local increases in pro-inflammatory mediators, e.g. Toll-like receptor (TLR) 4, nuclear factor-κB, tumour necrosis factor, platelet-activating factor (PAF), interleukin (IL)-18, interferon-gamma, IL-6, IL-8 and IL-1β. Deficiencies in counter-regulatory mechanisms, including IL-1 receptor antagonist (IL-1Ra), TLR9, PAF-acetylhydrolase, transforming growth factor beta (TGF-β)1&2, IL-10 and regulatory T cells likely facilitate a pro-inflammatory milieu in the NEC-afflicted intestine. There is insufficient evidence to conclude a predominance of an adaptive Th1-, Th2- or Th17-response in the disease. Our understanding of the accompanying regulation of systemic immunity remains poor; however, IL-1Ra, IL-6, IL-8 and TGF-β1 show promise as biomarkers. Here, we chart the emerging immunological landscape that underpins NEC by reviewing the involvement and potential clinical implications of innate and adaptive immune mediators and their regulation in NEC.

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坏死性小肠结肠炎的免疫学概况

坏死性小肠结肠炎 (NEC) 是一种不常见但具有破坏性的肠道炎症性疾病，主要影响早产儿。NEC 有时被称为新生儿重症监护病房的幽灵，因为它的发病是阴险的非特异性的，一旦疾病表现出来，对婴儿肠道造成的损害已经是灾难性的。随后的败血症和多器官衰竭导致高达 65% 的死亡率。NEC 的有效治疗方法的开发停滞不前，主要是因为我们对 NEC 发病机制缺乏了解。然而，很明显，NEC 是由严重失调的免疫系统驱动的。NEC 与促炎介质的局部增加有关，例如 Toll 样受体 (TLR) 4、核因子-κB、肿瘤坏死因子、血小板激活因子 (PAF)、白细胞介素 (IL)-18、干扰素-γ、IL-6、IL-8 和 IL-1β。反调节机制的缺陷，包括 IL-1 受体拮抗剂 (IL-1Ra)、TLR9、PAF-乙酰水解酶、转化生长因子 β (TGF-β)1&2、IL-10 和调节性 T 细胞可能促进受 NEC 影响的肠道中的促炎环境。没有足够的证据表明适应性 Th1、Th2 或 Th17 反应在该疾病中占优势。我们对伴随的全身免疫调节的理解仍然很差；然而，IL-1Ra、IL-6、IL-8 和 TGF-β1显示出作为生物标志物的前景。在这里，我们通过回顾先天性和适应性免疫介质的参与和潜在的临床意义及其在 NEC 中的调节来绘制支撑 NEC 的新兴免疫学格局。