Upper Airway Research Laboratory, Department of Otorhinolaryngology, Ghent University Hospital, Ghent, Belgium.
Eastern Virginia Medical School, Norfolk, Virginia, USA.
Int Forum Allergy Rhinol. 2022 Nov;12(11):1413-1423. doi: 10.1002/alr.22994. Epub 2022 Apr 11.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with eosinophilic tissue infiltration linked to type 2 inflammation and characterized by elevated levels of interleukin (IL)-5 and other type 2 inflammatory mediators. Although distinct and overlapping contributions of eosinophils and IL-5 to CRSwNP pathology are still being explored, they are both known to play an important role in NP inflammation. Eosinophils secrete numerous type 2 inflammatory mediators including granule proteins, enzymes, cytokines, chemokines, growth factors, lipids, and oxidative products. IL-5 is critical for the differentiation, migration, activation, and survival of eosinophils but is also implicated in the biological functions of mast cells, basophils, innate lymphoid cells, B cells, and epithelial cells. Results from clinical trials of therapeutics that target type 2 inflammatory mediators (including but not limited to anti-IL-5, anti-immunoglobulin-E, and anti-IL-4/13) may provide further evidence of how eosinophils and IL-5 contribute to CRSwNP. Finally, the association between eosinophilia/elevated IL-5 and greater rates of NP recurrence after endoscopic sinus surgery (ESS) suggests that these mediators may have utility as biomarkers of NP recurrence in diagnosing and assessing the severity of CRSwNP. This review provides an overview of eosinophil and IL-5 biology and explores the literature regarding the role of these mediators in CRSwNP pathogenesis and NP recurrence following ESS. Based on current published evidence, we suggest that although eosinophils play a key role in CRSwNP pathophysiology, IL-5, a cytokine that activates these cells, also represents a pertinent and effective treatment target in patients with CRSwNP.
慢性鼻-鼻窦炎伴鼻息肉(CRSwNP)通常与 2 型炎症相关的嗜酸性组织浸润有关,其特征是白细胞介素(IL)-5 和其他 2 型炎症介质水平升高。尽管嗜酸性粒细胞和 IL-5 对 CRSwNP 病理学的独特和重叠贡献仍在探索中,但它们都被认为在 NP 炎症中发挥重要作用。嗜酸性粒细胞分泌许多 2 型炎症介质,包括颗粒蛋白、酶、细胞因子、趋化因子、生长因子、脂质和氧化产物。IL-5 对嗜酸性粒细胞的分化、迁移、激活和存活至关重要,但也与肥大细胞、嗜碱性粒细胞、固有淋巴细胞、B 细胞和上皮细胞的生物学功能有关。针对 2 型炎症介质(包括但不限于抗 IL-5、抗免疫球蛋白 E 和抗 IL-4/13)的治疗药物临床试验结果可能进一步证明嗜酸性粒细胞和 IL-5 如何导致 CRSwNP。最后,嗜酸性粒细胞增多症/IL-5 升高与内镜鼻窦手术(ESS)后 NP 复发率较高之间的关联表明,这些介质可能作为 NP 复发的生物标志物在诊断和评估 CRSwNP 的严重程度方面具有一定的效用。这篇综述概述了嗜酸性粒细胞和 IL-5 的生物学特性,并探讨了关于这些介质在 CRSwNP 发病机制和 ESS 后 NP 复发中的作用的文献。基于目前已发表的证据,我们认为,尽管嗜酸性粒细胞在 CRSwNP 病理生理学中发挥关键作用,但激活这些细胞的细胞因子 IL-5 也是 CRSwNP 患者的一个相关且有效的治疗靶点。