Floris Ilaria, Appel Kurt, Rose Thorsten, Lejeune Beatrice
Clinical Affairs, Labo'Life France, Moutiers-Sous-Chantemerle, France,
VivaCell Biotechnology GmbH, Denzlingen, Germany.
J Inflamm Res. 2018 Oct 29;11:397-405. doi: 10.2147/JIR.S174326. eCollection 2018.
Tumor necrosis factor-α (TNF-α) and IL-1β are 2 pro-inflammatory cytokines known to be involved in rheumatic diseases. The therapeutic strategy used in micro-immunotherapy (MI) to reduce chronic inflammation and attenuate pain consists in mainly targeting these 2 cytokines. 2LARTH is a sublingually administered medicine consisting of lactose-saccharose globules impregnated with ethanolic preparations of immune mediators and nucleic acids at ultra-low doses.
The aim of the study is to explore the effect of the MI medicine on TNF-α and IL-1β secretion in human primary enriched monocytes exposed to lipopolysaccharide (LPS).
Placebo and active globules were diluted in culture medium to test 5 lactose-saccharose globules concentrations (from 1.75 to 22 mM). Freshly isolated enriched monocytes from 6 healthy donors were treated with or without LPS (10 ng/mL), LPS+ placebo, or LPS+ 2LARTH for 24 hours. IL-1β, TNF-α, and IL-6 release were evaluated by ELISA.
The medicine has significantly decreased the level of IL-1β secretion compared with placebo at these concentrations: 22 mM (<0.0001), 11 mM (=0.0086), 5.5 mM (= 0.0254), and compared with untreated LPS control at these concentrations: 22 mM, 11 mM (=0.0008), and 5.5 mM (=0.002). The effect of active globules on the reduction of TNF-α release is significant compared with placebo at these concentrations: 22 mM (=0.0018), 11 mM (=0.0005), 5.5 mM (=0.0136), and compared with untreated LPS control at these concentrations: 22 mM (=0.0021), 11 mM (=0.0017), 5.5 mM (=0.0052) and 2.25 mM (=0.0196). Besides, IL-6 secretion decreased compared with placebo at 22 mM (=0.0177) and 11 mM (=0.0031).
The results indicate that the tested product exerts significant anti-inflammatory effects on human LPS-stimulated monocytes.
肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）是已知参与风湿性疾病的两种促炎细胞因子。微免疫疗法（MI）中用于减轻慢性炎症和缓解疼痛的治疗策略主要针对这两种细胞因子。2LARTH是一种舌下给药的药物，由乳糖 - 蔗糖小球组成，小球中浸渍有超低剂量的免疫介质和核酸的乙醇制剂。
本研究旨在探讨MI药物对暴露于脂多糖（LPS）的人原代富集单核细胞中TNF-α和IL-1β分泌的影响。
将安慰剂和活性小球在培养基中稀释，以测试5种乳糖 - 蔗糖小球浓度（从1.75至22 mM）。来自6名健康供体的新鲜分离的富集单核细胞分别用或不用LPS（10 ng/mL）、LPS + 安慰剂或LPS + 2LARTH处理24小时。通过酶联免疫吸附测定（ELISA）评估IL-1β、TNF-α和IL-6的释放。
在这些浓度下，与安慰剂相比，该药物显著降低了IL-1β分泌水平：22 mM（<0.0001）、11 mM（=0.0086）、5.5 mM（=0.0254）；与未处理的LPS对照相比，在这些浓度下：22 mM、11 mM（=0.0008）和5.5 mM（=0.002）。在这些浓度下，与安慰剂相比，活性小球对降低TNF-α释放的作用显著：22 mM（=0.0018）、11 mM（=0.0005）、5.5 mM（=0.0136）；与未处理的LPS对照相比，在这些浓度下：22 mM（=0.0021）、11 mM（=分0.0017）、5.5 mM（=0.0052）和2.25 mM（=0.0196）。此外，与安慰剂相比，在22 mM（=0.0177）和11 mM（=0.0031）时IL-6分泌减少。
结果表明，所测试的产品对人LPS刺激的单核细胞具有显著的抗炎作用。
