Journal Articles
Publication Date
2-5-2024
Journal
Molecular Medicine
Abstract
BACKGROUND: Fluvoxamine is one of the selective serotonin reuptake inhibitors (SSRIs) that are regarded as the first-line drugs to manage mental disorders. It has been also recognized with the potential to treat inflammatory diseases and viral infection. However, the effect of fluvoxamine on autoimmune diseases, particularly type 1 diabetes (T1D) and the related cellular and molecular mechanisms, are yet to be addressed.
METHOD: Herein in this report, we treated NOD mice with fluvoxamine for 2 weeks starting from 10-week of age to dissect the impact of fluvoxamine on the prevention of type 1 diabetes. We compared the differences of immune cells between 12-week-old control and fluvoxamine-treated mice by flow cytometry analysis. to study the mechanism involved, we extensively examined the characteristics of CD4
RESULT: Fluvoxamine not only delayed T1D onset, but also decreased T1D incidence. Moreover, fluvoxamine-treated NOD mice showed significantly attenuated insulitis coupled with well-preserved β cell function, and decreased Th1 and Th17 cells in the peripheral blood, pancreatic lymph nodes (PLNs), and spleen. Mechanistic studies revealed that fluvoxamine downregulated glycolytic process by inhibiting phosphatidylinositol 3-kinase (PI3K)-AKT signaling, by which it restrained effector T (Teff) cell differentiation and production of proinflammatory cytokines.
CONCLUSION: Collectively, our study supports that fluvoxamine could be a viable therapeutic drug against autoimmunity in T1D setting.
Keywords
Mice, Humans, Animals, Diabetes Mellitus, Type 1, Mice, Inbred NOD, Fluvoxamine, Th17 Cells, Phosphatidylinositol 3-Kinases, Autoimmune Diseases, Th1 Cells
Included in
Endocrine System Diseases Commons, Endocrinology, Diabetes, and Metabolism Commons, Internal Medicine Commons, Public Health Commons