Group of Cell Therapy and Tissue Engineering, Research Institute on Health Sciences (IUNICS), University of the Balearic Islands, 07122 Palma de Mallorca, Spain.
Preclinical Research Department, Labo'Life España, 07330 Consell, Spain.
Int J Mol Sci. 2023 Jun 22;24(13):10484. doi: 10.3390/ijms241310484.
Periodontal therapies use immune mediators, but their side effects can increase with dosage. Micro-immunotherapy (MI) is a promising alternative that employs immune regulators at low and ultralow doses to minimize adverse effects. In this study, the effects of 5 capsules and the entire 10-capsule sequence of the sequential MI medicine (MIM-seq) were tested in two in vitro models of periodontitis. Firstly, human gingival fibroblasts (hGFs) exposed to interleukin (IL)-1β to induce inflammation were treated with five different capsules of MIM-seq for 3 days or with MIM-seq for 24 days. Subsequently, MIM-seq was analyzed in a 3D model of human tissue equivalent of gingiva (GTE) under the same inflammatory stimulus. Simultaneously, a non-IL-1β-treated control and a vehicle were included. The effects of the treatments on cytotoxicity, collagen deposition, and the secreted levels of IL-1α, IL-6, prostaglandin E2 (PGE2), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinases-1 (TIMP-1) were evaluated. None of the tested items were cytotoxic. The complete sequence of MIM-seq decreased PGE2 release and restored collagen deposition levels induced by IL-1β treatment in hGFs exposed to IL-1β. MIM-seq treatment restored collagen production levels in both models. These promising preclinical findings suggest that MIM-seq should be further investigated for periodontitis treatment.
牙周病治疗采用免疫调节剂，但随着剂量的增加，其副作用也会增加。微量免疫疗法（MI）是一种有前途的替代方法，它采用低剂量和超低剂量的免疫调节剂，以最大限度地减少不良反应。在这项研究中，在两种牙周炎体外模型中测试了 5 粒胶囊和整个 10 粒胶囊顺序的 MI 药物（MIM-seq）的作用。首先，将暴露于白细胞介素（IL）-1β以诱导炎症的人牙龈成纤维细胞（hGF）用 5 种不同的 MIM-seq 胶囊处理 3 天或用 MIM-seq 处理 24 天。随后，在相同的炎症刺激下，在人牙龈组织等效物（GTE）的 3D 模型中分析 MIM-seq。同时，包括非 IL-1β 处理对照和载体。评估处理对细胞毒性、胶原蛋白沉积以及分泌的白细胞介素-1α、白细胞介素-6、前列腺素 E2（PGE2）、基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制剂-1（TIMP-1）水平的影响。测试的项目均无细胞毒性。MIM-seq 全序列降低了 PGE2 的释放，并恢复了暴露于 IL-1β的 hGF 中由 IL-1β 处理诱导的胶原蛋白沉积水平。MIM-seq 处理恢复了两种模型中的胶原蛋白产生水平。这些有前景的临床前发现表明，MIM-seq 应该进一步研究用于牙周病治疗。
