几种微免疫疗法制剂的细胞抗炎作用的特别关注：关于肠道、免疫轴相关和神经元炎症背景的考量

Special Focus on the Cellular Anti-Inflammatory Effects of Several Micro-Immunotherapy Formulations: Considerations Regarding Intestinal-, Immune-Axis-Related- and Neuronal-Inflammation Contexts.

作者信息

Jacques Camille, Floris Ilaria

机构信息

Preclinical Research Department, Labo'Life France, Nantes, France.

出版信息

J Inflamm Res. 2022 Dec 13;15:6695-6717. doi: 10.2147/JIR.S389614. eCollection 2022.

INTRODUCTION

Chronic inflammation is a pernicious underlying status, well-known for its contribution to the progressive development of various diseases. In this regard, Micro-immunotherapy (MI) might be a promising therapeutic strategy. MI employs low doses (LD) and ultra-low doses (ULD) of immune regulators in their formulations. In particular, as both IL-1β and TNF-α are often used at ULD in MI medicines (MIM), a special emphasis has been made on formulations that include these factors in their compositions.

METHODS

Several in vitro models have been employed in order to assess the effects of two unitary MIM consisting of ULD of IL-1β and TNF-α (u-MIM-1 and u-MIM-2, respectively), and four complex MIM (c-MIM-1, -2, -3 and -4) characterized by the presence of ULD of IL-1β and TNF-α amongst other factors. Thus, we first investigated the anti-inflammatory effects of u-MIM-1 and u-MIM-2 in a model of inflamed colon carcinoma cells. In addition, the anti-inflammatory potential of c-MIM-1, -2, -3 and -4, was assessed in in vitro models of intestinal and neuronal inflammation.

RESULTS

The results revealed that u-MIM-1 and u-MIM-2 both induced a slight decrease in the levels of IL-1β and TNF-α transcripts. Regarding the c-MIMs' effects, c-MIM-1 displayed the capability to restore the altered transepithelial electrical resistance in inflamed-HCoEpiC cells. Moreover, c-MIM-1 also slightly increased the expression of the junction-related protein claudin-1, both at the mRNA and protein levels. In addition, our in vitro investigations on c-MIM-2 and c-MIM-3 revealed their immune-modulatory effects in LPS-inflamed human monocytes, macrophages, and granulocytes, on the secretion of cytokines such as TNF-α, PGE2, and IL-6. Finally, c-MIM-4 restored the cell viability of LPS/IFN-γ-inflamed rat cortical neurons, while reducing the secretion of TNF-α in rat glial cells.

DISCUSSION

Our results shed the light on the potential role of these MIM formulations in managing several chronic inflammation-related conditions.

引言

慢性炎症是一种有害的潜在状态，因其在各种疾病的进展发展中所起的作用而广为人知。在这方面，微免疫疗法（MI）可能是一种有前景的治疗策略。MI在其制剂中使用低剂量（LD）和超低剂量（ULD）的免疫调节剂。特别是，由于白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）在MI药物（MIM）中常以超低剂量使用，因此对其成分中包含这些因子的制剂给予了特别关注。

方法

采用了几种体外模型，以评估两种分别由超低剂量的IL-1β和TNF-α组成的单一MIM（分别为u-MIM-1和u-MIM-2）以及四种以超低剂量的IL-1β和TNF-α以及其他因子为特征的复合MIM（c-MIM-1、-2、-3和-4）的效果。因此，我们首先在炎症性结肠癌细胞模型中研究了u-MIM-1和u-MIM-2的抗炎作用。此外，在肠道和神经元炎症的体外模型中评估了c-MIM-1、-2、-3和-4的抗炎潜力。

结果

结果显示，u-MIM-1和u-MIM-2均导致IL-1β和TNF-α转录水平略有下降。关于复合MIM的效果，c-MIM-1显示出恢复炎症性人结肠上皮细胞（HCoEpiC）中改变的跨上皮电阻的能力。此外，c-MIM-1在mRNA和蛋白质水平上也略微增加了紧密连接相关蛋白claudin-1的表达。此外，我们对c-MIM-2和c-MIM-3的体外研究揭示了它们在脂多糖（LPS）诱导炎症的人单核细胞、巨噬细胞和粒细胞中对TNF-α、前列腺素E2（PGE2）和IL-6等细胞因子分泌的免疫调节作用。最后，c-MIM-4恢复了LPS/干扰素-γ（IFN-γ）诱导炎症的大鼠皮质神经元的细胞活力，同时减少了大鼠胶质细胞中TNF-α的分泌。