Wright E D, Frenkiel S, Al-Ghamdi K, Ghaffar O, Small P, Troutt T, Tavernier J, Hamid Q
Meakins-Christie Laboratories, Montreal, Quebec, Canada.
Otolaryngol Head Neck Surg. 1998 Apr;118(4):490-5. doi: 10.1177/019459989811800411.
Chronic sinusitis and its associated eosinophilic infiltrate are believed to be mediated, at least in part, by the upregulation of Th-2 cytokines, including interleukin-4, interleukin-5, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interleukin-4 is involved in IgE production and in eosinophil recruitment through upregulation of vascular cell adhesion molecule-1. Interleukin-5 and GM-CSF are involved in eosinophil growth and survival. The aim of this study was to investigate the expression of receptors for these cytokines in the sinus mucosa of subjects with chronic sinusitis. Using the technique of in situ hybridization to detect specific cytokine receptor messenger RNA, we studied the sinus mucosa of subjects with nonallergic chronic sinusitis, subjects with allergic chronic sinusitis, subjects with allergic chronic sinusitis treated with topical steroids, and normal controls. Our data demonstrate higher expression of interleukin-4 receptor in subjects with allergic chronic sinusitis than in controls (p < 0.001) and higher expression of interleukin-5 receptor in both subjects with nonallergic chronic sinusitis and subjects with allergic chronic sinusitis than in controls (p < 0.001, p < 0.001). The expression of interleukin-4 receptor and interleukin-5 receptor was higher in subjects with allergic chronic sinusitis than in subjects with nonallergic chronic sinusitis (p < 0.001). GM-CSF receptor expression was also found to be higher in subjects with allergic chronic sinusitis and subjects with nonallergic chronic sinusitis than in controls (p < 0.001, p < 0.001). In contrast to interleukin-4 receptor and interleukin-5 receptor, however, expression of GM-CSF receptor was higher in subjects with nonallergic chronic sinusitis than in subjects with allergic chronic sinusitis (p < 0.001). In subjects with allergic chronic sinusitis treated with topical corticosteroids, the expression of interleukin-4 receptor and interleukin-5 receptor messenger RNA levels was significantly lower than levels in patients with allergic chronic sinusitis who were not taking topical steroids (p < 0.001, p < 0.001). Steroid treatment had no effect on GM-CSF receptor messenger RNA expression. In conclusion, our data support a role for Th-2 cytokine receptors in the pathophysiology of chronic sinusitis. Further, our data lend support to the theory that differential activation of distinct cytokine pathways mediates inflammation in chronic sinusitis depending on whether there is associated allergy. Finally, treatment with topical corticosteroids has been demonstrated in chronic sinusitis to downregulate receptors for interleukin-4 and interleukin-5.
慢性鼻窦炎及其相关的嗜酸性粒细胞浸润被认为至少部分是由Th-2细胞因子上调介导的，这些细胞因子包括白细胞介素-4、白细胞介素-5和粒细胞-巨噬细胞集落刺激因子（GM-CSF）。白细胞介素-4通过上调血管细胞黏附分子-1参与免疫球蛋白E的产生和嗜酸性粒细胞的募集。白细胞介素-5和GM-CSF参与嗜酸性粒细胞的生长和存活。本研究的目的是调查这些细胞因子受体在慢性鼻窦炎患者鼻窦黏膜中的表达。我们使用原位杂交技术检测特定细胞因子受体信使核糖核酸，研究了非过敏性慢性鼻窦炎患者、过敏性慢性鼻窦炎患者、接受局部类固醇治疗的过敏性慢性鼻窦炎患者以及正常对照者的鼻窦黏膜。我们的数据表明，过敏性慢性鼻窦炎患者白细胞介素-4受体的表达高于对照组（p < 0.001），非过敏性慢性鼻窦炎患者和过敏性慢性鼻窦炎患者白细胞介素-5受体的表达均高于对照组（p < 0.001，p < 0.001）。过敏性慢性鼻窦炎患者白细胞介素-4受体和白细胞介素-5受体的表达高于非过敏性慢性鼻窦炎患者（p < 0.001）。GM-CSF受体的表达在过敏性慢性鼻窦炎患者和非过敏性慢性鼻窦炎患者中也高于对照组（p < 0.001，p < 0.001）。然而，与白细胞介素-4受体和白细胞介素-5受体不同，非过敏性慢性鼻窦炎患者GM-CSF受体的表达高于过敏性慢性鼻窦炎患者（p < 0.001）。在接受局部皮质类固醇治疗的过敏性慢性鼻窦炎患者中，白细胞介素-4受体和白细胞介素-5受体信使核糖核酸水平的表达明显低于未使用局部类固醇的过敏性慢性鼻窦炎患者（p < 0.001，p < 0.001）。类固醇治疗对GM-CSF受体信使核糖核酸的表达没有影响。总之，我们的数据支持Th-2细胞因子受体在慢性鼻窦炎病理生理学中的作用。此外，我们的数据支持这样一种理论，即不同细胞因子途径的差异激活介导慢性鼻窦炎的炎症，这取决于是否存在相关过敏。最后，在慢性鼻窦炎中已证明局部皮质类固醇治疗可下调白细胞介素-4和白细胞介素-5的受体。
