关键词: Burkholderia cepacia complex IL-17F MMP TNFα cystic fibrosis glucose metabolism disturbances inflammation lymphocyte sensitivity to steroid suppression

Mesh : Humans Cystic Fibrosis / complications microbiology mortality Child Male Female Adolescent Biomarkers / blood Burkholderia Infections / mortality immunology Cross-Sectional Studies Cytokines / blood metabolism Sputum / microbiology Child, Preschool Prospective Studies Disease Progression Burkholderia cepacia Burkholderia cepacia complex

来  源:   DOI:10.3389/fcimb.2024.1374318   PDF(Pubmed)

Abstract:
UNASSIGNED: In current literature there are only scarce data on the host inflammatory response during Burkholderia cepacia complex (Bcc) persistence. The primary objective of the present research was to carry out cross-sectional analyses of biomarkers and evaluate disease progression in cystic fibrosis (CF) patients with chronic Bcc infection and pathogen-free ones. The secondary aim was to assess prospectively overall survival of the study participants during up to 8 years of follow-up.
UNASSIGNED: The study included 116 paediatric patients with CF; 47 CF patients were chronically infected with Bcc, and 69 individuals were Bcc free. Plasma and sputum biomarkers (neutrophil elastase, MMP-8, MMP-9, MMP-12, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IL-22, IL-23, IL-17, IFN-γ, TGFβ1, TNF-α) were analysed using commercially available kits. Besides, inhibitory effect of dexamethasone on proliferative response of PHA-stimulated peripheral blood lymphocytes had been assessed.
UNASSIGNED: Bcc infected patients did not differ from Bcc free ones in demographic and clinical parameters, but demonstrated an increased rate of glucose metabolism disturbances and survival disadvantage during prolong follow-up period. Biomarkers analyses revealed elevated TNF-α and reduced IL-17F levels in sputum samples of Bcc infected patients. These patients also demonstrated improvement of peripheral blood lymphocyte sensitivity to steroid treatment and reduction in plasma pro-inflammatory (IL-17F and IL-18) and anti-inflammatory (TGFβ1 and IL-10) cytokine concentrations.
UNASSIGNED: Reduction in IL-17F levels may have several important consequences including increase in steroid sensitivity and glycemic control disturbances. Further investigations are needed to clarify the role of IL-17 cytokines in CF complication development. Low plasma TGFβ1 and IL-10 levels in Bcc infected group may be a sign of subverted activity of regulatory T cells. Such immune alterations may be one of the factors contributing to the development of the cepacia syndrome.
摘要:
在目前的文献中,关于洋葱伯克霍尔德氏菌(Bcc)持续期间宿主炎症反应的数据很少。本研究的主要目的是对生物标志物进行横断面分析,并评估患有慢性Bcc感染和无病原体感染的囊性纤维化(CF)患者的疾病进展。次要目的是评估研究参与者在长达8年的随访期间的前瞻性总体生存率。
该研究包括116例小儿CF患者;47例CF患者慢性感染Bcc,69个人无Bcc。血浆和痰生物标志物(中性粒细胞弹性蛋白酶,MMP-8,MMP-9,MMP-12,IL-2,IL-4,IL-6,IL-8,IL-10,IL-18,IL-22,IL-23,IL-17,IFN-γ,使用市售试剂盒分析TGFβ1,TNF-α)。此外,已经评估了地塞米松对PHA刺激的外周血淋巴细胞增殖反应的抑制作用。
Bcc感染患者在人口统计学和临床参数上与无Bcc感染患者没有差异,但在延长的随访期内,葡萄糖代谢紊乱和生存劣势的发生率增加。生物标志物分析显示,Bcc感染患者的痰液样本中TNF-α水平升高,IL-17F水平降低。这些患者还表现出外周血淋巴细胞对类固醇治疗的敏感性的改善以及血浆促炎(IL-17F和IL-18)和抗炎(TGFβ1和IL-10)细胞因子浓度的降低。
降低IL-17F水平可能有几个重要的后果,包括增加类固醇敏感性和血糖控制紊乱。需要进一步的研究来阐明IL-17细胞因子在CF并发症发展中的作用。Bcc感染组中血浆TGFβ1和IL-10水平低可能是调节性T细胞活性破坏的标志。这种免疫改变可能是导致洋葱综合征发展的因素之一。
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