Instituto de Inmunología Clínica y Experimental Rosario (IDICER), CONICET-UNR, Rosario, Santa Fe, Argentina.
Facultad de Ciencias Médicas, Universidad Nacional de Rosario, Rosario, Santa Fe, Argentina.
PLoS One. 2021 Sep 10;16(9):e0257214. doi: 10.1371/journal.pone.0257214. eCollection 2021.
Our earlier studies in tuberculosis (TB) patients indicate that in those where the process evolves to a larger pulmonary involvement, the immune endocrine response may promote an unfavorable environment. Chronic infectious diseases, and their persistent proinflammatory response, may affect mucosal barriers integrity favoring the translocation of gastrointestinal bacteria, leading to an increase of circulating lipopolysaccharides (LPS). Consequently, we quantified LPS levels in TB patients, with different degrees of pulmonary involvement, and controls (Co) and analyzed the possible relationship between LPS and inflammatory mediators i.e., C reactive protein (CRP), interleukin 6 (IL-6) and Interferon-gamma (IFN-γ), Erythrocyte Sedimentation Rate (ESR), steroid hormones (Cortisol and Dehydroepiandrosterone, DHEA), and inflammatory transcripts from peripheral blood mononuclear cells (IL-1β, IL-6, IFN-γ). LPS was assessed by the Limulus amoebocyte lysate assay and the ELISA technique was used to quantify hormones and cytokines in the plasma samples. Cytokine transcripts from PBMC were evaluated by qRT-PCR. Non-parametric tests were used. LPS levels were increased in TB patients, as did levels of CRP, IL-6, IFN-γ, cortisol and ESR. Severe patients had the highest amounts of circulating LPS; with moderate and severe cases showing much higher levels of CRP, ESR, IL-6, IFN-γ and cortisol/DHEA ratio, as an endocrine imbalance. Only in PBMC from severe cases was mRNA for IL-1β increased. Correlation analysis showed that levels of LPS from severe patients were positively associated with IL-6 and IFN-γ plasma concentrations and with IL-1β transcripts, while IL-6 had a positive correlation with the cortisol/DHEA ratio. The higher levels of circulating LPS during progressive TB may emerge as a contributing factor for the persistence of the greater immune endocrine imbalance distinctive of advanced disease, which might suggest a vicious cycle among LPS, inflammation and endocrine imbalance.
我们之前的结核病（TB）患者研究表明，在病情进展为更广泛的肺部受累的患者中，免疫内分泌反应可能会导致不利的环境。慢性传染病及其持续的促炎反应可能会影响黏膜屏障的完整性，有利于胃肠道细菌的易位，导致循环内毒素（LPS）增加。因此，我们定量检测了不同程度肺部受累的 TB 患者和对照者（Co）的 LPS 水平，并分析了 LPS 与炎症介质（即 C 反应蛋白（CRP）、白细胞介素 6（IL-6）和干扰素-γ（IFN-γ）、红细胞沉降率（ESR）、类固醇激素（皮质醇和脱氢表雄酮，DHEA）以及外周血单个核细胞（IL-1β、IL-6、IFN-γ）中的炎症转录本之间的可能关系。LPS 通过鲎变形细胞溶解物测定法进行评估，并且使用 ELISA 技术来定量血浆样品中的激素和细胞因子。通过 qRT-PCR 评估 PBMC 中的细胞因子转录本。使用非参数检验。TB 患者的 LPS 水平升高，CRP、IL-6、IFN-γ、皮质醇和 ESR 水平也升高。严重患者的循环 LPS 含量最高；中度和重度患者的 CRP、ESR、IL-6、IFN-γ 和皮质醇/DHEA 比值明显升高，表现出内分泌失衡。仅在严重病例的 PBMC 中增加了 IL-1β 的 mRNA。相关性分析表明，严重患者的 LPS 水平与血浆中 IL-6 和 IFN-γ 的浓度以及 IL-1β 的转录物呈正相关，而 IL-6 与皮质醇/DHEA 比值呈正相关。在进展性 TB 期间，循环中 LPS 的更高水平可能是导致更严重疾病中持续存在更大的免疫内分泌失衡的一个促成因素，这可能提示 LPS、炎症和内分泌失衡之间存在恶性循环。
