Treatment with AM3 restores defective T-cell function in COPD patients
Treatment with AM3 restores defective T-cell function in COPD patients
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DOI：
10.1378/chest.129.3.527
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发表时间：
2006-03-01
期刊：
影响因子：
9.6
通讯作者：
Alvarez-Mon, M
中科院分区：
文献类型：
--
作者：
Reyes, E;Prieto, AF;Alvarez-Mon, M
背景：淋巴细胞改变与COPD患者急性呼吸道感染患病率增加相关。AM3是一种口服免疫调节剂，可使COPD患者外周血自然杀伤细胞和吞噬细胞的功能缺陷正常化，并改善其健康相关的生活质量。目的：描述COPD患者T细胞室的假定系统异常，并研究AN 13是否可以恢复此类异常。设计：该研究是一项在COPD患者队列中进行的随机、前瞻性、双盲、安慰剂对照试验。结果也进行了比较，非吸烟者和前吸烟者的健康对照subjects.Setting：门诊部的四家hospital.Patients：70 COPD患者随机接受AM3或安慰剂口服连续90天。36名健康的非吸烟者和36名健康的戒烟者作为对照组。测量：在基线和治疗结束时评估外周血单核细胞（PBMC）增殖和白细胞介素（IL）-2，IL-4，IL-12 p40，肿瘤坏死因子-α和干扰素（IFN）-γ蛋白的产生对T细胞多克隆有丝分裂原的反应。COPD患者的增殖反应明显降低。IFN-γ产生减少是细胞因子测量结果中唯一的缺陷，并且在COPD患者中选择性地观察到，但在不吸烟者和前吸烟者健康对照受试者中未观察到。用AM3治疗显著恢复了PBMC对多克隆有丝分裂原的增殖应答，并显著促进了这些患者中刺激的IFN-γ产生。这些增殖反应的正常化与外周血单核细胞、CD 3+、CD 4+、CD 8+细胞或任何主要幼稚/记忆/活化T细胞亚群数量的显著变化无关。在AM3研究臂中IFN-γ产生的增加与每CD 8 + T细胞产生的IFN-γ分子的平均数增加相关。结论：COPD患者的PBMC显示出明确的功能性T淋巴细胞异常，这是由AM3治疗挽救的。
Background: Lymphocyte alterations have been associated with an increased prevalence of acute respiratory infections in COPD patients. AM3 is an oral immunomodulator that normalizes the defective functions of peripheral blood natural killer and phagocytic cells in COPD patients and improves their health-related quality of life.Objectives: To characterize putative systemic abnormalities of the T-cell compartment in COPD patients, and to investigate whether AN13 can restore such abnormalities.Design: The study was a randomized, prospective, double-blind, placebo-controlled trial in a cohort of COPD patients. The results were also compared to those of nonsmoker and ex-smoker healthy control subjects.Setting: Outpatient departments of four hospitals.Patients: Seventy COPD patients were randomized to receive either AM3 or a placebo orally for 90 consecutive days. Populations of 36 healthy nonsmokers and 36 healthy ex-smokers were used as control subjects.Measurements: Peripheral blood mononuclear cell (PBMC) proliferation and production of interleukin (IL)-2, IL-4, IL-12p40, tumor necrosis factor-alpha, and interferon (IFN)-gamma proteins in response to the T-cell polyclonal mitogens were assessed at baseline and at the end of treatment.Results: The proliferative response was significantly decreased in COPD patients. Decreased production of IFN-gamma was the only defect in the profiles of the cytokine measures, and was selectively observed in COPD patients, but not in nonsmoker and ex-smoker healthy control subjects. Treatment with AM3 significantly restored the PBMC proliferative response to polyclonal mitogens and significantly promoted stimulated IFN-gamma production in these patients. The normalization of these proliferative responses was not related to significant variations in the numbers of peripheral blood monocytes, CD3+, CD4+, CD8+ cells or of any major naive/ memory/activated T-cell subset. The increased IFN-gamma production in the AM3 study arm was associated with an increase in the mean of number of IFN-gamma molecules produced per CD8+ T cells.Conclusions: PBMCs of COPD patients showed clear functional T-lymphocyte abnormalities that are rescued by AM3 treatment.