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口服盐酸毛果芸香碱前后干燥综合征患者全唾液中分泌型免疫球蛋白A及细胞因子水平:一项初步研究

s-IgA and cytokine levels in whole saliva of Sjögren's syndrome patients before and after oral pilocarpine hydrochloride administration: a pilot study.

作者信息

Rhodus N, Dahmer L, Lindemann K, Rudney J, Mathur A, Bereuter J

机构信息

Division of Oral Medicine, University of Minnesota, Minneapolis, USA.

出版信息

Clin Oral Investig. 1998 Dec;2(4):191-6. doi: 10.1007/s007840050069.

Abstract

Previous investigations have found elevated levels of s-IgA in the parotid saliva and normal levels in submandibular saliva of patients with Sjögren's syndrome (SS). Fox et al. also found elevated levels of cytokines (i.e., IL-2 and IL-6) in serum, salivary epithelial cells and parotid saliva of patients with SS. The oral administration of pilocarpine hydrochloride stimulates whole and parotid salivary flow. The purpose of this study was to determine the levels of s-IgA and IL-2 and IL-6 in whole saliva before and after administration of pilocarpine hydrochloride in SS subjects. Ten definitively diagnosed SS subjects were enrolled in the study, as were ten controls (C). The mean age was 57.2 years and all subjects were female. Whole unstimulated saliva (WUS) was collected by standard techniques for 5 min, after which the volume and flow rate were determined (mean WUS: SS = 0.047 vs C = 0.480 ml/min). Samples were centrifuged and the immunoglobulin analysis performed on the supernatants by immunoreactivity in a double-sandwich technique as previously described by Rudney et al. Cytokine analysis was performed similarly utilizing commercially available kits from R&D Systems. The results as analyzed by pairwise t-tests revealed comparable levels of s-IgA in the saliva of the SS patients, as compared to controls at baseline (means +/- SEM: SS-IgA = 348.1 +/- 82.0 vs C-IgA = 284.0 +/- 65.1 micrograms/ml; NS). Whole salivary flow was significantly increased (328%) in the SS subject group 60 min after the administration of 5 mg pilocarpine hydrochloride (means +/- SEM: 0.0472 +/- 0.017 vs 0.1546 +/- 0.054 ml/min; P < 0.01). There was no significant change in the concentration of s-IgA in the SS subject group following the pilocarpine dose (means +/- SEM: SS-IgA = 439.9 +/- 121.2 microliters/ml; P = NS). There were elevated levels of IL-2 in the saliva of four out of the ten and IL-6 in two out of the ten SS patients, as compared to controls (means +/- SEM: SS-IL-2 = 127.8 +/- 11.4 vs C-IL-2 = 30.8 +/- 1.6 pg/ml and SS-IL-6 = 41.4 +/- 7.1 vs C-11.6 +/- 2.8 pg/ml). There was also a significant decrease in the concentration of IL-2 in the same four out of ten SS subjects following the pilocarpine dose (means +/- SEM: SS-IL-2 = 32.4 +/- 10.3; P < 0.01). These preliminary results indicate that s-IgA levels do not change with increased salivary flow following the administration of pilocarpine hydrochloride in patients with Sjögren's syndrome. While cytokines are elevated in the whole saliva of some SS patients, a decrease in IL-2 concentration may occur with increased salivary flow.

摘要

以往的研究发现,干燥综合征(SS)患者腮腺唾液中的分泌型免疫球蛋白A(s-IgA)水平升高,而颌下唾液中的水平正常。福克斯等人还发现,SS患者的血清、唾液上皮细胞和腮腺唾液中的细胞因子(如白细胞介素-2和白细胞介素-6)水平升高。口服盐酸毛果芸香碱可刺激全唾液和腮腺唾液的分泌。本研究的目的是确定SS患者口服盐酸毛果芸香碱前后全唾液中s-IgA、白细胞介素-2和白细胞介素-6的水平。本研究纳入了10例确诊的SS患者和10例对照(C)。平均年龄为57.2岁,所有受试者均为女性。采用标准技术收集5分钟的非刺激性全唾液(WUS),然后测定其体积和流速(平均WUS:SS = 0.047 vs C = 0.480 ml/分钟)。将样本离心,采用鲁德尼等人先前描述的双夹心技术,通过免疫反应对上清液进行免疫球蛋白分析。细胞因子分析同样使用R&D Systems公司的市售试剂盒进行。通过配对t检验分析结果显示,与基线时的对照组相比,SS患者唾液中s-IgA的水平相当(均值±标准误:SS-IgA = 348.1±82.0 vs C-IgA = 284.0±65.1微克/毫升;无显著性差异)。在5毫克盐酸毛果芸香碱给药后60分钟,SS受试者组的全唾液流速显著增加(328%)(均值±标准误:0.0472±0.017 vs 0.1546±0.054毫升/分钟;P < 0.01)。在给予毛果芸香碱剂量后,SS受试者组中s-IgA的浓度没有显著变化(均值±标准误:SS-IgA = 439.9±121.2微升/毫升;P = 无显著性差异)。与对照组相比,10例SS患者中有4例唾液中的白细胞介素-2水平升高,10例中有2例白细胞介素-6水平升高(均值±标准误:SS-白细胞介素-2 = 127.8±11.4 vs C-白细胞介素-2 = 30.8±1.6皮克/毫升,SS-白细胞介素-6 = 41.4±7.1 vs C-11.6±2.8皮克/毫升)。在这10例SS受试者中的4例中,给予毛果芸香碱剂量后白细胞介素-2的浓度也显著降低(均值±标准误:SS-白细胞介素-2 = 32.4±10.3;P < 0.01)。这些初步结果表明,在干燥综合征患者中,口服盐酸毛果芸香碱后唾液流速增加时,s-IgA水平不会改变。虽然一些SS患者的全唾液中细胞因子升高,但随着唾液流速增加,白细胞介素-2浓度可能会降低。

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