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

Mauricio Castillo-Salazar,Sara García-Jiménez,Adrián Hernández-Diazcouder,Fausto Sánchez-Muñoz,Rashidi Springall Del Villar,Cairo Toledano-Jaimes,Carlos Mojica-Cardoso,Germán Bernal-Fernández,Gabriel Navarrete-Vázquez

doi:10.3390/biom11121817

Mauricio Castillo-Salazar, Sara García-Jiménez + Show 7 more

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https://doi.org/10.3390/biom11121817

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Abstract

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.

Highlights

Introduction published maps and institutional affilType 2 diabetes (T2D) is a chronic degenerative inflammatory disorder characterized by insulin dysfunction and chronic hyperglycemia [1]
Conclusions expected because IL-2 is produced by activated T lymphocytes and is essential for growth, NTZ is positioned as a new the treatment ofcrucial
Our findings show that NTZ produced a significant decrease in the level of IL-6 supernatants from cultured peripheral blood mononuclear cells (PBMCs), while the concentration of IL-6 was re-established with antibodies

Summary

Introduction

Type 2 diabetes (T2D) is a chronic degenerative inflammatory disorder characterized by insulin dysfunction and chronic hyperglycemia [1]. Federation (IDF) reported 463 million people with diabetes worldwide, with a prevalence of more than 9%, 1 in 2 cases of which had not yet been diagnosed, and it is projected that there will be 700 million cases in 2045. T2D represents 90% of all the cases of diabetes, and its inadequate control leads to cardiovascular disease, kidney failure, neuropathy, and lower limb amputation, resulting in frequent hospitalizations and premature death [2]. There are many pharmacological strategies for treating T2D, new therapies are still needed. Chronic systemic inflammation is recognized as a causative factor of the pathogenesis in T2D [3,4], producing abnormalities in the immune response [5], such as proliferation and activation of T lymphocytes and macrophages; functional deterioration of B lymphocytes and natural killer cells; and decreased chemotaxis, phagocytosis, and iations.

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