IL-4 fails to regulate in vitro beryllium-induced cytokines in berylliosis
IL-4 fails to regulate in vitro beryllium-induced cytokines in berylliosis
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DOI：
10.1183/09031936.01.17304030
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发表时间：
2001-03-01
影响因子：
24.3
通讯作者：
Newman, LS
中科院分区：
文献类型：
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作者：
Maier, LA;Sawyer, RT;Newman, LS
慢性铍病（CBD）患者的支气管肺泡灌洗（BAL）细胞已被用于评估铍特异性免疫应答和潜在的免疫治疗。小檗碱从BAL细胞诱导干扰素-γ（IFN-γ）、白介素-2（IL-2）、肿瘤坏死因子-α（TNF-α）、白介素-6（IL-6）和白介素-10（IL-10）。IL-2和重组人IL-10的抗体能够部分抑制铍刺激的免疫应答。为了获得BAL细胞，需要支气管镜检查，这为患者提供了风险和有限数量的细胞来研究免疫应答。因此，研究的目的是确定1）用铍刺激的CBD外周血单核细胞（PBMN）是否会产生与BAL细胞相似的细胞因子模式，以及2）这种应答是否可以通过白细胞介素-4（IL-4）调节。CBD和正常人的PBMN和BAL细胞用和不用硫酸铍刺激。为了调节这种抗原刺激的反应，我将rHu IL-4加入到未刺激和铍刺激的细胞中。通过酶联免疫吸附测定（ELISA）从细胞上清液中测定IFN-γ、IL-2、TNF-α、IL-6和IL-10细胞因子浓度，而使用聚合酶链反应（PCR）评估IL-4信使核糖核酸（mRNA）。与未刺激的CBD PBMN相比，铍刺激显著的IFN-γ、TNF-rr、IL-2、IL-6和IL-10产生。这种反应与CBD BAL细胞刺激的反应相似，尽管幅度低得多。在CBD和对照PBMN中发现低水平的IL-4 mRNA，其不随铍刺激而增加。铍刺激的细胞因子水平没有通过添加IL-4而降低，IL-4不能下调来自CBD BAL细胞的任何这些铍刺激的细胞因子或增加来自CBD PBMN或BAL细胞的IL-4 mRNA，因此不太可能是CBD中的免疫调节剂。VAS得出结论，慢性铍病外周血单核细胞提供了研究铍刺激的免疫应答的模型。白细胞介素-L1不能下调任何铍刺激的细胞因子，使其不太可能成为慢性铍病的治疗候选者。
Bronchoalveolar lavage (BAL) cells from patients with chronic beryllium disease (CBD) have been used to evaluate the beryllium-specific immune response and potential immunotherapeuties. Beryllium induces interferon-gamma (IFN-gamma), interleukin-2 IL-2), tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-10 (IL-10) from BAL cells. An antibody to IL-2 and recombinant human (rHu) IL-10 is able to partially suppress the beryllium-stimulated immune response. To obtain BAL cells, bronchoscopy is required, providing risk to the patient and a limited number of cells to study the immune response, As a result, the objectives of the study were to determine 1) whether CBD peripheral blood mononuclear cells (PBMNs) stimulated with beryllium would produce a similar cytokine pattern as BAL cells, and 2) whether this response could be modulated by interleukin-4 (IL-4), an immunomodulatory cytokine.CBD and normal individuals' PBMN and BAL cells were stimulated with and without beryllium sulfate. To modulate this antigen-stimulated response, me added rHu IL-4 to the unstimulated and beryllium-stimulated cells. IFN-gamma, IL-2, TNF-alpha, IL-6 and IL-10 cytokine concentrations were determined from cell supernatants by enzyme-linked immunosorbent assays (ELISA), while IL-4 messenger ribonucleic acid (mRNA) was assessed using polymerase chain reaction (PCR).Beryllium did not stimulate any of these cytokines from normal PBMNs, Increasing levels of IL-6 and TNF-alpha were produced constituitively by CBD PBMNs over time. Compared to the unstimulated CBD PBMNs, beryllium stimulated significant IFN-gamma, TNF-rr, IL-2, IL-6 and IL-10 production. This response was similar to that stimulated from CBD BAL cells, although of a much lower magnitude, Low levels of IL-4 mRNA were found in CBD and control PBMNs, which were not increased with beryllium stimulation. The beryllium-stimulated cytokine levels were not decreased by the addition of IL-4, IL-4 was unable to downregulate any of these beryllium-stimulated cytokines from CBD BAL cells or increase IL-4 mRNA from either CBD PBMN or BAL cells, and thus is an unlikely immunomodulatory agent in CBD.From the data, it,vas concluded that chronic beryllium disease peripheral blood mononuclear cells provide a model to study the beryllium-stimulated immune response. Interleukin-Ll's inability to downregulate any of the beryllium-stimulated cytokines makes it an unlikely therapeutic candidate in chronic beryllium disease.