Dipartimento di Patologia Sperimentale, University of Pisa, Via San Zeno 39, I-56127 Pisa, Italy.
Immunol Lett. 2012 Jan 30;141(2):204-9. doi: 10.1016/j.imlet.2011.10.005. Epub 2011 Oct 14.
Increasing evidence links pulmonary pathology to cytokines determining an inflammatory environment in the lung. Detection of cells secreting specific cytokines in BALF could be helpful as a diagnostic tool but which cytokines to choose among their great variety may be the first question to solve. The aim of this study was to investigate the Th1, Th2 and Th17 cytokine profile in whole cells within the human bronchoalveolar lavage fluid (BALF) by flow cytometry, with a focus on interleukin (IL)-17-producing cells, in order to assess which cytokines might lend themselves as markers of disease in future studies. BALF and paired peripheral blood samples were collected from 52 patients admitted to hospital for pulmonary pathologies. Cells obtained from BALF and peripheral blood were incubated in vitro in the absence or presence of appropriate stimuli and analyzed for intracellular content of IL-4, -10, -12, -17, interferon (IFN)γ and tumor necrosis factor (TNF)α in association to expression of either HLA-DR or CD4. IL-17-secreting cells were further characterized. Production of IL-17 by unstimulated BALF cells could be detected in 2 of the 32 patients that could be examined; upon PMA/IM stimulation in vitro, IL-17 was produced by varying percentages of lymphocytes, mostly memory CD4(+) cells, in all BALF samples. IL-4 could be detected in a relatively high proportion of unstimulated HLA-DR(+/-), SSC(hi) cells, most probably granulocytes; IL-10 could be found mostly in macrophages in a number of the BALF samples analyzed. Finally, IFNγ and TNFα were only produced by lymphocytes after in vitro stimulation. This study shows that T cells producing IL-17 can be found in the lung of respiratory patients in the absence of ex vivo stimulation, making IL-17 a good candidate marker of specific pathologies of the lung. Upon stimulation, IL-17 production was accounted for by CD4(+) CD45RO(+) cells. Other cytokines are also discussed. An interesting cytokine secretion profile found in BALF from a patient with rheumatoid lung disease is also reported.
越来越多的证据表明，肺部病理学与细胞因子有关，这些细胞因子决定了肺部的炎症环境。在 BALF 中检测到分泌特定细胞因子的细胞可能有助于作为诊断工具，但在众多细胞因子中选择哪些作为诊断工具可能是首先要解决的问题。本研究旨在通过流式细胞术研究全细胞中的 Th1、Th2 和 Th17 细胞因子谱，重点研究白细胞介素（IL）-17 产生细胞，以评估哪些细胞因子可能成为未来研究中疾病的标志物。收集了 52 名因肺部疾病住院的患者的 BALF 和配对外周血样本。从 BALF 和外周血中获得的细胞在体外于无刺激或适当刺激的条件下孵育，并分析细胞内 IL-4、-10、-12、-17、干扰素（IFN）γ和肿瘤坏死因子（TNF）α的含量，同时分析 HLA-DR 或 CD4 的表达情况。进一步对 IL-17 分泌细胞进行了特征分析。在可检测的 32 名患者中的 2 名患者中，可检测到未刺激的 BALF 细胞产生的 IL-17；体外经 PMA/IM 刺激后，所有 BALF 样本中均有不同比例的淋巴细胞，主要是记忆 CD4(+)细胞，产生 IL-17。在未刺激的 HLA-DR(+/-)、SSC(hi)细胞中，很可能是粒细胞中，可检测到相对较高比例的 IL-4；在分析的许多 BALF 样本中，可发现 IL-10 主要存在于巨噬细胞中。最后，只有在体外刺激后，淋巴细胞才会产生 IFNγ和 TNFα。本研究表明，在没有体外刺激的情况下，可在呼吸患者的肺部中发现产生 IL-17 的 T 细胞，这使 IL-17 成为肺部特定疾病的良好候选标志物。刺激后，CD4(+) CD45RO(+)细胞负责 IL-17 的产生。还讨论了其他细胞因子。还报告了从患有类风湿肺疾病的患者的 BALF 中发现的有趣的细胞因子分泌谱。
