Jacques Camille, Marchand Flora, Chatelais Mathias, Floris Ilaria
Preclinical Research Department, Labo'Life France, Pescalis-Les Magnys, Moncoutant-sur-Sevre, 79320, France.
ProfileHIT, Sainte-Pazanne, 44680, France.
J Inflamm Res. 2024 Feb 21;17:1161-1181. doi: 10.2147/JIR.S445053. eCollection 2024.
Micro-immunotherapy (MI) is a therapeutic option employing low doses (LD) and ultra-low doses (ULD) of cytokines and immune factors to help the organism at modulating the immune responses. In an overpowering inflammatory context, this strategy may support the restoration of the body's homeostasis, as the active ingredients of MI medicines' (MIM) could boost or slow down the physiological functions of the immune cells. The aim of the study is to evaluate for the first time the in vitro anti-inflammatory properties of some actives employed by the MIM of interest in several human immune cell models.
In the first part of the study, the effects of the actives from the MIM of interest were assessed from a molecular standpoint: the expression of HLA-II, interleukin (IL)-2, and the secretion of several other cytokines were evaluated. In addition, as mitochondrial metabolism is also involved in the inflammatory processes, the second part of the study aimed at assessing the effects of these actives on the mitochondrial reactive oxygen species (ROS) production and on the mitochondrial membrane potential.
We showed that the tested actives decreased the expression of HLA-DR and HLA-DP in IFN-γ-stimulated endothelial cells and in LPS-treated-M1-macrophages. The tested MIM slightly reduced the intracellular expression of IL-2 in CD4 and CD8 T-cells isolated from PMA/Iono-stimulated human PBMCs. Additionally, while the secretion of IL-2, IL-10, and IFN-γ was diminished, the treatment increased IL-6, IL-9, and IL-17A, which may correspond to a "Th17-like" secretory pattern. Interestingly, in PMA/Iono-treated PBMCs, we reported that the treatment reduced the ROS production in B-cells. Finally, in PMA/Iono-treated human macrophages, we showed that the treatment slightly protected the cells from early cell death/apoptosis.
Overall, these results provide data about the molecular and functional anti-inflammatory effects of several actives contained in the tested MIM in immune-related cells, and their impact on two mitochondria-related processes.
微免疫疗法（MI）是一种治疗方法，它使用低剂量（LD）和超低剂量（ULD）的细胞因子和免疫因子来帮助机体调节免疫反应。在炎症反应强烈的情况下，该策略可能有助于恢复机体的稳态，因为微免疫疗法药物（MIM）的活性成分可以增强或减缓免疫细胞的生理功能。本研究的目的是首次在几种人类免疫细胞模型中评估某些感兴趣的微免疫疗法药物所使用的活性成分的体外抗炎特性。
在研究的第一部分，从分子角度评估了感兴趣的微免疫疗法药物中活性成分的作用：评估了HLA-II、白细胞介素（IL）-2的表达以及其他几种细胞因子的分泌。此外，由于线粒体代谢也参与炎症过程，研究的第二部分旨在评估这些活性成分对线粒体活性氧（ROS）产生和线粒体膜电位的影响。
我们发现，在干扰素-γ刺激的内皮细胞和脂多糖处理的M1巨噬细胞中，测试的活性成分降低了HLA-DR和HLA-DP的表达。测试的微免疫疗法药物略微降低了从佛波酯/离子霉素刺激的人外周血单个核细胞中分离出的CD4和CD8 T细胞中IL-2的细胞内表达。此外，虽然IL-2、IL-IO和干扰素-γ的分泌减少，但该处理增加了IL-6、IL-9和IL-17A的分泌，这可能对应一种 “类Th17” 分泌模式。有趣的是，在佛波酯/离子霉素处理的外周血单个核细胞中，我们发现该处理降低了B细胞中的ROS产生。最后，在佛波酯/离子霉素处理的人巨噬细胞中，我们表明该处理略微保护细胞免于早期细胞死亡/凋亡。
总体而言，这些结果提供了有关测试的微免疫疗法药物中所含几种活性成分在免疫相关细胞中的分子和功能抗炎作用的数据，以及它们对两个线粒体相关过程的影响。
