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间质性膀胱炎患者尿液细胞因子水平的初步研究:卡介苗膀胱灌注是否通过改变膀胱免疫状态来治疗间质性膀胱炎?

Preliminary study on urinary cytokine levels in interstitial cystitis: does intravesical bacille Calmette-Guérin treat interstitial cystitis by altering the immune profile in the bladder?

作者信息

Peters K M, Diokno A C, Steinert B W

机构信息

Department of Urology, William Beaumont Hospital, Royal Oak, Michigan 48073, USA.

出版信息

Urology. 1999 Sep;54(3):450-3. doi: 10.1016/s0090-4295(99)00162-4.

DOI:10.1016/s0090-4295(99)00162-4
PMID:10475352
Abstract

OBJECTIVES

To obtain preliminary urinary cytokine data on subjects with active interstitial cystitis (IC), subjects with IC in remission after bacille Calmette-Guérin (BCG), and control (non-IC) subjects. IC is a severe, debilitating bladder disease of unknown etiology and no cure. In controlled clinical trials, intravesical BCG has been shown to be an effective and durable treatment for IC. The durability of this treatment led us to speculate on the mechanism by which intravesical BCG may treat IC. Evidence exists that IC may be mediated by an abnormal immune profile within the bladder. Intravesical BCG is known to stimulate the immune system of the bladder.

METHODS

Fresh voided urine was collected from 15 subjects with active IC, 9 subjects with IC who received intravesical BCG and had been in remission for an average of 2.6 years, and 11 non-IC subjects. The urine was immediately centrifuged, aliquoted, and frozen in liquid nitrogen. At the time of urine collection, a validated IC questionnaire was completed. The enzyme-linked immunosorbent assay technique was used to determine levels of urinary cytokines interleukin (IL)-2, IL-4, IL-6, IL-8, IL-10, IL-12, tumor necrosis factor (TNF), human granulocyte-macrophage colony stimulating factor (hGM-CSF), IL-1beta, and interferon-gamma (IFN-gamma).

RESULTS

Cytokines IL-4, IL-10, IL-12, TNF, hGM-CSF, IL-1beta, and IFN-gamma were not detected. Significant elevations in symptom scores and IL-2, IL-6, and IL-8 were found in the urine of subjects with active IC compared with subjects with IC in remission and control subjects. The urinary cytokine levels and symptom scores were identical in the IC group who had received BCG and the control group.

CONCLUSIONS

Elevations in symptom scores and urinary cytokine levels were seen in subjects with active IC, suggesting an abnormal immune profile in this disease. Subjects with IC in remission after receiving BCG had identical cytokine levels and symptom scores as non-IC control subjects. Intravesical BCG may be effective in treating IC by correcting an aberrant immune imbalance in the bladder, leading to long-term symptomatic improvement. A prospective study is ongoing to further investigate the role of the immune system in IC.

摘要

目的

获取活动性间质性膀胱炎(IC)患者、卡介苗(BCG)治疗后病情缓解的IC患者以及对照(非IC)受试者的尿细胞因子初步数据。IC是一种病因不明且无法治愈的严重致残性膀胱疾病。在对照临床试验中,膀胱内灌注BCG已被证明是治疗IC的一种有效且持久的方法。这种治疗的持久性促使我们推测膀胱内灌注BCG治疗IC的机制。有证据表明,IC可能由膀胱内异常的免疫特征介导。已知膀胱内灌注BCG可刺激膀胱免疫系统。

方法

收集15例活动性IC患者、9例接受膀胱内灌注BCG且平均缓解2.6年的IC患者以及11例非IC受试者的新鲜晨尿。尿液立即离心、分装并在液氮中冷冻。在收集尿液时,完成一份经过验证的IC问卷。采用酶联免疫吸附测定技术测定尿细胞因子白细胞介素(IL)-2、IL-4、IL-6、IL-8、IL-10、IL-12、肿瘤坏死因子(TNF)、人粒细胞巨噬细胞集落刺激因子(hGM-CSF)、IL-1β和干扰素-γ(IFN-γ)的水平。

结果

未检测到细胞因子IL-4、IL-10、IL-12、TNF、hGM-CSF、IL-1β和IFN-γ。与病情缓解的IC患者和对照受试者相比,活动性IC患者尿液中的症状评分以及IL-2、IL-6和IL-8显著升高。接受BCG治疗的IC组患者的尿细胞因子水平和症状评分与对照组相同。

结论

活动性IC患者的症状评分和尿细胞因子水平升高,表明该疾病存在异常的免疫特征。接受BCG治疗后病情缓解的IC患者的细胞因子水平和症状评分与非IC对照受试者相同。膀胱内灌注BCG可能通过纠正膀胱内异常的免疫失衡来有效治疗IC,从而实现长期症状改善。一项前瞻性研究正在进行,以进一步探究免疫系统在IC中的作用。

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