变应性鼻炎患者血清缺氧诱导因子-1α和促红细胞生成素的变化：与 Th 炎症特征及疾病合并症的相关性。
Changes in serum hypoxia-inducible factor-1α and erythropoietin in allergic rhinitis patients: Correlation with the Th inflammatory profile and disease comorbidities.
机构信息
Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Jouf University, Sakaka, Saudi Arabia.
Department of Pathology, College of Medicine, Jouf University, Sakaka, Saudi Arabia.
出版信息
Int J Immunopathol Pharmacol. 2023 Jan-Dec;37:3946320231196745. doi: 10.1177/03946320231196745.
OBJECTIVES
The balance between proinflammatory IFN-γ Th1 vs. the anti-inflammatory allergy-mediating IL-4-heralded Th2 reactions is pivotal in IgE-mediated allergic rhinitis (AR). Hypoxia-Inducible Factor (HIF)-1α is inducible by hypoxia and various cytokines. HIF-1α activates different anti-pathogen and allergic immune cells. This cross-sectional study assessed the changes in serum HIF-1α and its dependent erythropoietin (EPO) levels among hospital-characterized AR patients. Type of the immune reaction, Th1 vs. Th2, was stratified based on the calculated IL-4/IFN-γ direct ratio, after being measured using specific ELISA assays.
METHODS
147 AR patients (83 males/64 females), and age-, BMI-, and gender-matched 24 healthy controls (13 males/11 females) were sequentially enrolled at ENT Unit, Prince Muteb General Hospital, Sakaka, Saudi Arabia. Measurement of serum parameters was carried out using specific ELISA assays.
RESULTS
Contrary to the majority of previous publications, all controls and the majority of patients ( = 137/147) exhibited naive Th0 immune response. IFN-γ and HIF-1α levels were greater in controls than in patients (168.9 ± 173.9 vs 108 ± 94.5 pg/mL; <.012) and controls had a lower IL-4/IFN-ratio (2.439 ± 0.897 vs 3.33 ± 1.19; <.001) than patients. The HIF-1α results disagree with earlier studies. Due to the wide inter-individual variations, serum IL-4 and EPO levels in controls were non-significantly higher than patients. Lower IL-4 levels (267.3 ± 79.95 vs 353.4 ± 320.6 pg/mL; < .01) and the ratio (2.814 ± 1.335 vs 3.431 ± 1.137; < .05) were associated with obstructive sleep apnea. Lower ratio was also associated with inferior turbinate hypertrophy (3.051 ± 1.026 vs 3.787 ± 1.310; < .001). EPO and IL-4 levels were lower in patients with deviated nasal septum (66.69 ± 26.81 vs 84.24 ± 61.5 pg/mL; < .021; and 299.5 ± 137.3 vs 391.1 ± 52.780 pg/mL; < .001, respectively). Significant correlations were found between the recorded levels and AR comorbidities.
CONCLUSION
These results confirmed a pathogenic implication for HIF-1α and IFN-γ in AR that warranted future bigger and longitudinal studies.
目的
促炎细胞因子 IFN-γ 引发的 Th1 反应与抗炎过敏反应介导的 IL-4 引发的 Th2 反应之间的平衡在 IgE 介导的过敏性鼻炎 (AR) 中至关重要。缺氧诱导因子 (HIF)-1α 可被缺氧和各种细胞因子诱导。HIF-1α 可激活不同的抗病原体和过敏性免疫细胞。本横断面研究评估了在沙特阿拉伯 Sakaka 的王子 Muteb 总医院耳鼻喉科就诊的 AR 患者中，血清 HIF-1α 及其依赖的促红细胞生成素 (EPO) 水平的变化。根据特定的 ELISA 测定，计算出的 IL-4/IFN-γ 直接比值将免疫反应分为 Th1 与 Th2 型。
方法
连续纳入 147 名 AR 患者（83 名男性/64 名女性）和年龄、BMI 和性别匹配的 24 名健康对照者（13 名男性/11 名女性）。采用特定的 ELISA 检测试剂盒测量血清参数。
结果
与大多数先前的研究结果相反，所有对照者和大多数患者（=137/147）均表现为幼稚的 Th0 免疫反应。与患者相比，对照者的 IFN-γ 和 HIF-1α 水平更高（168.9 ± 173.9 与 108 ± 94.5 pg/mL；<.012），且对照者的 IL-4/IFN-比值更低（2.439 ± 0.897 与 3.33 ± 1.19；<.001）。HIF-1α 结果与早期研究不一致。由于个体间差异较大，对照组的血清 IL-4 和 EPO 水平略高于患者。较低的 IL-4 水平（267.3 ± 79.95 与 353.4 ± 320.6 pg/mL；<.01）和比值（2.814 ± 1.335 与 3.431 ± 1.137；<.05）与阻塞性睡眠呼吸暂停相关。较低的比值也与下鼻甲肥大有关（3.051 ± 1.026 与 3.787 ± 1.310；<.001）。鼻中隔偏曲患者的 EPO 和 IL-4 水平更低（66.69 ± 26.81 与 84.24 ± 61.5 pg/mL；<.021；299.5 ± 137.3 与 391.1 ± 52.780 pg/mL；<.001）。研究还发现记录水平与 AR 合并症之间存在显著相关性。
结论
这些结果证实了 HIF-1α 和 IFN-γ 在 AR 中的致病作用，这需要进一步开展更大规模和纵向研究。
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