硝唑尼特对 2 型糖尿病患者外周血单个核细胞发挥免疫调节作用。

Nitazoxanide Exerts Immunomodulatory Effects on Peripheral Blood Mononuclear Cells from Type 2 Diabetes Patients.

机构信息

Pharmacy Faculty, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico.

Immunology Department, Instituto Nacional de Cardiología Ignacio Chávez, Tlalpan, Mexico City 14080, Mexico.

出版信息

Biomolecules. 2021 Dec 2;11(12):1817. doi: 10.3390/biom11121817.

BACKGROUND

Type 2 diabetes (T2D) is a low-grade inflammatory condition with abnormalities in the immune response mediated by T lymphocytes and macrophages. Drug repositioning for immunomodulatory molecules is an attractive proposal for treating T2D. Nitazoxanide (NTZ) is a broad-spectrum drug with promising immunomodulatory effects. Thus, we investigated the immunomodulatory effect of NTZ on peripheral blood mononuclear cells (PBMCs) from patients with T2D.

METHODS

Fifty patients with T2D were selected, and the proliferative response of T lymphocytes and the M1/M2 ratio of macrophages post cell culture were evaluated by flow cytometry, as well as measuring the concentration of cytokines by ELISA and the relative expression of microRNAs (miRNAs) related to the immune response by real-time PCR.

RESULTS

NTZ exerts an inhibitory effect on the cell proliferation of T lymphocytes stimulated with anti-CD3 and anti-CD28 antibodies without modifying cell viability, and significant decreases in the supernatant concentrations of interleukin (IL)-1β, IL-2, IL-6, IL-10, and IL-12. Furthermore, NTZ negatively regulates the relative expression of miR-155-5p without changes in miR-146a-5p. The M1/M2 ratio of monocytes/macrophages decreased the M1 and increased the M2 subpopulation by NTZ.

CONCLUSIONS

Our results suggest that NTZ exerts immunomodulatory effects on PBMCs from T2D patients, and shows potential alternative therapeutic benefits.

背景

2 型糖尿病（T2D）是一种低度炎症状态，其免疫反应异常与 T 淋巴细胞和巨噬细胞有关。免疫调节分子的药物再利用是治疗 T2D 的一种有吸引力的建议。硝唑尼特（NTZ）是一种具有有前途的免疫调节作用的广谱药物。因此，我们研究了 NTZ 对 T2D 患者外周血单个核细胞（PBMC）的免疫调节作用。

方法

选择 50 例 T2D 患者，通过流式细胞术评估 T 淋巴细胞的增殖反应和巨噬细胞的 M1/M2 比值，并通过 ELISA 测量细胞培养后细胞因子的浓度，通过实时 PCR 测量与免疫反应相关的 microRNAs（miRNAs）的相对表达。

结果

NTZ 对抗 CD3 和抗 CD28 抗体刺激的 T 淋巴细胞的细胞增殖具有抑制作用，而不改变细胞活力，并且显著降低白细胞介素（IL）-1β、IL-2、IL-6、IL-10 和 IL-12 的上清液浓度。此外，NTZ 负调节 miR-155-5p 的相对表达，而 miR-146a-5p 不变。单核细胞/巨噬细胞的 M1/M2 比值通过 NTZ 降低 M1 并增加 M2 亚群。