Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Key Laboratory of Otolaryngology Head and Neck Surgery, Capital Medical University, Beijing 100730, China.
Chin Med J (Engl). 2009 Sep 20;122(18):2149-54.
Otitis media with effusion (OME) is a disease with complicated pathogeneses which are not clearly known. Increasing interest has been focused on immunological cells, cytokines and their roles in chronic inflammatory states. This study was designed to disclose the existence and roles of interleukin-10 (IL-10) and transforming growth factor beta1 (TGF-beta1) in the cause of OME in adults, and to investigate the probable role of Foxp3(+)CD4(+)CD25(+) T cells in OME.
The concentrations of IL-10 and TGF-beta1 in the middle ear effusions (MEEs) and plasmas of 36 adults (45 ears) with OME were measured by means of enzyme linked immunosorbent assay (ELISA). As contrast, the concentrations of IL-10 and TGF-beta1 in the plasma of 30 normal volunteers were measured using the same method. Furthermore, the proportion of Foxp3(+)CD4(+)CD25(+) T cells in CD4(+) T cells of blood was tested by flow cytometry.
(1) The concentrations of IL-10 in all MEEs and plasmas of the chronic OME patients were higher than those in patients with acute OME (both P < 0.05), so was TGF-beta1 (both P < 0.01). The concentration of IL-10 in MEEs was significantly higher than that in plasmas, not only in acute OME (P < 0.01), but also in chronic OME (P < 0.01). In chronic OME, the concentration of TGF-beta1 in MEEs had no statistical difference with those in plasmas of the same patients. However, the concentration of TGF-beta1 in plasmas of patients with chronic OME was significantly higher than that in plasmas of normal volunteers (P < 0.01). (2) The concentrations of IL-10 and TGF-beta1 in MEEs of the patients who had been treated more than once were higher than those MEEs of the patients who were treated for the first time, respectively (P < 0.05, P < 0.01). The level of TGF-beta1 in plasmas of the patients who had been treated more than once was higher than in those of the patients who were treated firstly (P < 0.05), while the level of IL-10 in plasmas had no difference. The concentration of IL-10 in mucoid MEEs was higher than those in serous ones (P < 0.05), while TGF-beta1 had no statistical difference between mucoid and serous MEEs (P > 0.05). The concentration of IL-10 in MEEs had a strong correlation with the duration of the illness (r = 0.547, P < 0.01). The same correlation was also found between the concentration of TGF-beta1 in MEEs and the times patients being treated (r = 0.579, P < 0.01). (3) The proportion of Foxp3(+)CD4(+)CD25(+)T/CD4(+) T cells in the blood of chronic OME was not only significantly higher than that in the acute OME (P < 0.01), but also higher than that in normal volunteers (P < 0.01). In chronic OME, there was a correlation between the proportion of Foxp3(+)CD4(+)CD25(+) T/CD4(+) T cells in the blood and the concentration of IL-10 in the plasmas (r = 0.602, P < 0.05).
IL-10 and TGF-beta1, as two important immunoregulatory mediators, participate in middle ear inflammatory response, especially in chronic course of OME in adults. Foxp3(+)CD4(+)CD25(+) T cells may play some immunoregulatory roles in the course of this disease.
分泌性中耳炎(OME)是一种发病机制复杂、尚不明确的疾病。人们对免疫细胞、细胞因子及其在慢性炎症状态中的作用越来越感兴趣。本研究旨在揭示白细胞介素-10(IL-10)和转化生长因子-β1(TGF-β1)在成人OME发病机制中的存在和作用,并探讨Foxp3(+)CD4(+)CD25(+)T 细胞在 OME 中的可能作用。
采用酶联免疫吸附试验(ELISA)检测 36 例(45 耳)OME 成人患者中耳积液(MEEs)和血浆中 IL-10 和 TGF-β1 的浓度,以 30 例正常志愿者的血浆作为对照。此外,采用流式细胞术检测血液中 Foxp3(+)CD4(+)CD25(+)T 细胞在 CD4(+)T 细胞中的比例。
(1)慢性 OME 患者的 MEEs 和血浆中 IL-10 浓度均高于急性 OME 患者(均 P < 0.05),TGF-β1 浓度亦高于急性 OME 患者(均 P < 0.01)。慢性 OME 患者 MEEs 中 IL-10 浓度明显高于血浆,急性 OME 患者亦是如此(均 P < 0.01)。慢性 OME 患者 MEEs 中 TGF-β1 浓度与患者同次血浆中 TGF-β1 浓度无统计学差异,但慢性 OME 患者血浆中 TGF-β1 浓度明显高于正常志愿者(P < 0.01)。(2)多次治疗患者的 MEEs 中 IL-10 和 TGF-β1 浓度均高于首次治疗患者(均 P < 0.05,P < 0.01),多次治疗患者的血浆 TGF-β1 浓度高于首次治疗患者(P < 0.05),IL-10 浓度无统计学差异。黏蛋白性 MEEs 中 IL-10 浓度高于浆液性 MEEs(P < 0.05),而 TGF-β1 在黏蛋白性和浆液性 MEEs 之间无统计学差异(P > 0.05)。MEEs 中 IL-10 浓度与病程时间呈强相关(r = 0.547,P < 0.01),MEEs 中 TGF-β1 浓度与患者治疗次数呈强相关(r = 0.579,P < 0.01)。(3)慢性 OME 患者血液中 Foxp3(+)CD4(+)CD25(+)T/CD4(+)T 细胞的比例不仅明显高于急性 OME(P < 0.01),而且明显高于正常志愿者(P < 0.01)。慢性 OME 患者血液中 Foxp3(+)CD4(+)CD25(+)T/CD4(+)T 细胞的比例与血浆中 IL-10 浓度呈正相关(r = 0.602,P < 0.05)。
IL-10 和 TGF-β1 作为两种重要的免疫调节介质,参与中耳炎症反应,特别是成人 OME 的慢性过程。Foxp3(+)CD4(+)CD25(+)T 细胞可能在该疾病的发生发展中发挥一定的免疫调节作用。