Fang Kai-Min, Chiu Yen-Ling, Hong Ruo-Wei, Cheng Ping-Chia, Cheng Po-Wen, Liao Li-Jen
Department of Nursing, Oriental Institute of Technology, College of Healthcare and Management, New Taipei City 220, Taiwan.
Department of Otolaryngology Head and Neck Surgery, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan.
Biomedicines. 2024 Apr 29;12(5):980. doi: 10.3390/biomedicines12050980.
The prevention of postoperative recurrence after endoscopic sinus surgery (ESS) relies on targeting specific pathological mechanisms according to individuals' immunological profiles. However, essential biomarkers and biological characteristics of difficult-to-treat chronic rhinosinusitis (CRS) patients are not well-defined. The aim of this study was to explore the immunologic profiles of subgroups of CRS patients and determine the specific cytokines responsible for recalcitrant or recurrent CRS with nasal polyposis (rCRSwNP). We used 30 cytokine antibody arrays to determine the key cytokines related to recurrent polypogenesis. Enzyme-linked immunosorbent assay (ELISA) experiments were conducted to assess the levels of these key cytokines in 78 patients. Polymorphonuclear leukocytes (PMNs) isolated from nasal polyps were challenged with specific cytokines to examine the levels of enhanced interleukin (IL)-8 production. Finally, we used immunohistochemistry (IHC) staining to check for the presence and distribution of the biomarkers within nasal polyps. A cytokine antibody array revealed that IL-8, IL-13, IL-15, and IL-20 were significantly higher in the recalcitrant CRSwNP group. Subsequent ELISA screening showed a stepwise increase in tissue IL-8 levels in the CHR, CRSsNP, and CRSwNP groups. PMNs isolated from nine CRSwNP cases all demonstrated enhanced IL-8 production after IL-15 treatment. IHC staining was labeled concurrent IL-8 and IL-15 expression in areas of prominent neutrophil infiltration. Our results suggest that IL-15 within the sinonasal mucosa plays a crucial role in promoting IL-8 secretion by infiltrating PMNs in recalcitrant nasal polyps. In addition, we propose a novel therapeutic strategy targeting the anti-IL-15/IL-8 axis to treat CRS with nasal polyposis.
内镜鼻窦手术（ESS）后预防术后复发依赖于根据个体免疫状况针对特定病理机制。然而，难治性慢性鼻窦炎（CRS）患者的关键生物标志物和生物学特征尚未明确界定。本研究的目的是探索CRS患者亚组的免疫状况，并确定导致伴有鼻息肉的顽固性或复发性CRS（rCRSwNP）的特定细胞因子。我们使用30种细胞因子抗体阵列来确定与息肉复发相关的关键细胞因子。进行酶联免疫吸附测定（ELISA）实验以评估78例患者中这些关键细胞因子的水平。用特定细胞因子刺激从鼻息肉中分离出的多形核白细胞（PMN），以检测白细胞介素（IL）-8产生增加的水平。最后，我们使用免疫组织化学（IHC）染色来检查鼻息肉内生物标志物的存在和分布。细胞因子抗体阵列显示，顽固性CRSwNP组中IL-8、IL-13、IL-15和IL-20显著升高。随后的ELISA筛查显示，CHR、CRSsNP和CRSwNP组中组织IL-8水平呈逐步升高。从9例CRSwNP病例中分离出的PMN在IL-15处理后均显示IL-8产生增加。IHC染色显示在中性粒细胞浸润明显的区域同时有IL-8和IL-15表达。我们的结果表明，鼻窦黏膜内的IL-15在促进顽固性鼻息肉中浸润的PMN分泌IL-8方面起关键作用。此外，我们提出了一种针对抗IL-15/IL-8轴的新型治疗策略来治疗伴有鼻息肉的CRS。
