Department of Respiration Medicine, Chongqing Prevention and Treatment Center for Occupational Diseases, No. 301, Nancheng Avenue, Nanan District, Chongqing, China.
Department of Respiration Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Med Hypotheses. 2019 Oct;131:109319. doi: 10.1016/j.mehy.2019.109319. Epub 2019 Jul 20.
We hypothesize that exogenous intrapleural injection of interleukin-27 may improve outcome and prognosis in patients with tuberculous pleural effusion (TPE). Studies have found that the balance of Th1/Th2 determines the development trend of TPE. High concentrations of IFN-γ and TNF-α in pleural effusion are associated with pleural adhesion in patients with TPE. Interleukin-27 is a member of the IL-12 family, and IL-27 has a dual regulatory effect on Th1 immunity. On one hand, IL-27 can promote the initial CD4+ T cell proliferation by inducing the expression of T-bet, IL-12Rβ2 and ICAM-1 in the initial CD4+ T cells, and also promote its differentiation into Th1 cells and IFN-γ production in the early infection. On the other hand, in the case of high Th1 polarization, IL-27 induced STAT3 phosphorylation and inhibited TNF and IL-12 production in activated peritoneal macrophages, indicating a novel feedback mechanism by which IL-27 can modulate excessive inflammation, thereby preventing damage to the body caused by excessive immune response. Studies haves confirmed that after stimulation of antigen by mononuclear cells in TPE, the Th1 and Th2 cell subsets and Th1/Th2 ratio markedly increase, and the increase of Th1 is more obvious than that of Th2. Therefore, compared to patients with TPE in the high-level IL-27 group, we hypothesized that pleural effusion is absorbed more slowly, pleural thickening is more obvious, pleural adhesions are more extensive, and the incidence of thoracic collapse is higher in the low-level IL-27 group under the same conditions of anti-tuberculosis treatment. However, exogenous intrapleural injection of IL-27 may induce Stat3 phosphorylation and inhibit TNF and IL-12 production, finally reduces the secretion of IFN-γ and TNF-α. This negative regulation inhibits the excessive inflammatory reaction caused by tuberculosis infection, reduces pleural adhesion, pleural thickening and local pleural tissue damage, thereby improving the prognosis of patients.
我们假设向结核性胸腔积液(TPE)患者的胸腔内注入外源性白细胞介素-27(IL-27)可能会改善其结局和预后。研究发现,Th1/Th2 平衡决定了 TPE 的发展趋势。TPE 患者胸腔积液中 IFN-γ 和 TNF-α 浓度较高与胸腔粘连有关。白细胞介素-27 是白细胞介素-12 家族的一员,对 Th1 免疫具有双重调节作用。一方面,IL-27 通过诱导初始 CD4+T 细胞表达 T-bet、IL-12Rβ2 和 ICAM-1,促进初始 CD4+T 细胞的初始增殖,并在早期感染时促进其向 Th1 细胞分化和 IFN-γ 的产生。另一方面,在高 Th1 极化的情况下,IL-27 诱导激活的腹腔巨噬细胞中 STAT3 磷酸化并抑制 TNF 和 IL-12 的产生,这表明 IL-27 可以通过一种新的反馈机制调节过度炎症,从而防止过度免疫反应对机体造成的损害。研究证实,在 TPE 中的单核细胞被抗原刺激后,Th1 和 Th2 细胞亚群及其 Th1/Th2 比值明显增加,且 Th1 的增加比 Th2 更明显。因此,与高水平 IL-27 组的 TPE 患者相比,我们假设在相同的抗结核治疗条件下,低水平 IL-27 组胸腔积液吸收更慢,胸腔增厚更明显,胸腔粘连更广泛,胸廓塌陷发生率更高。然而,外源性胸腔内注射 IL-27 可能会诱导 Stat3 磷酸化并抑制 TNF 和 IL-12 的产生,最终减少 IFN-γ 和 TNF-α 的分泌。这种负性调节抑制了由结核感染引起的过度炎症反应,减少了胸腔粘连、胸腔增厚和局部胸膜组织损伤,从而改善了患者的预后。