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Long-Term Effects of Low-Dose Naltrexone on Immunomodulatory Properties of Human Adipose-Derived Mesenchymal Stem Cells

Document Type : Original Article

Authors

1 Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran.

2 Department of Immunology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.

3 Cancer and Immunology Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.

4 Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

5 Zoonosis Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran.

Abstract

Background: Low-dose naltrexone (LDN) is involved in the treatment of inflammatory and immune system diseases and can affect immune cells. Mesenchymal stem cells (MSCs) are known for their immunomodulatory effects and the potential for the treatment of certain types of autoimmune diseases.
Objective: To investigate the long-term effects of LDN on human adipose-derived mesenchymal stem cells (ASCs) to see how their immunomodulatory properties are affected and also how LDN-treated ASCs interact with other immune cells present in peripheral blood mononuclear cells (PBMCs).
Methods: After 14 days of treatment, the ability of LDN-treated ASCs to modulate PBMC proliferation in a two-way mixed lymphocyte reaction (MLR) model was assessed using XTT. The relative expression of IDO, PD-L1, COX-2, HGF genes, and the level of IL-6 and TGF-β cytokines were measured in IFN-γ stimulated and unstimulated ASCs (treated and not treated cells) using real-time PCR and ELISA respectively.
Results: Unstimulated ASCs treated with 10-8 M Naltrexone (10-8 M NTX) showed higher levels of TGF-β, compared with the controls (P<0.05). Stimulated ASCs treated with 10-6 M NTX showed elevated expression of IDO, PD-L1 genes, and IL-6 level (P<0.05).
Conclusion: Our results demonstrated that various LDN concentrations have dissimilar effects on ASCs’ immunomodulatory properties. A higher LDN concentration induced an alteration in the immunomodulatory features of ASCs.

Keywords

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Iranian Journal of Immunology
Volume 20, Issue 2
June 2023
Pages 219-231
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