Agomelatine for Sjögren's syndrome: a study on its therapeutic effects and mechanisms

Sjogren's Syndrome (SS) is an autoimmune disease characterized mainly by xerostomia (dry mouth), xerophthalmia (dry eyes) and damage of immune system. Recent studies have found that SS patients frequently experience neuropsychiatric symptoms such as depression and fatigue, suggesting potential underlying mechanisms involving complex immune-neural interactions. However, current therapeutic strategies targeting this immune-neuropsychiatric axis remain limited. Agomelatine (AGO), a novel antidepressant classified as a melatonin (MLT) receptor agonist and a 5-HT2C receptor antagonist, has yet to be fully investigated for its immunomodulatory potential and therapeutic application in SS.

This study explores the immune-neuropsychiatric interaction in SS using Non-Obese Diabetic (NOD) mice, and investigates the therapeutic potential of AGO, highlighting its anti-inflammatory and immunomodulatory effects.

NOD mice were divided into blank control, hydroxychloroquine (HCQ, a basic immune regulatory drug), MLT, and AGO groups; ICR mice served as healthy controls. All received intraperitoneal injections for 4 weeks. Behavioral tests (open field and tail suspension) were conducted. Flow cytometric analysis was performed to systematically evaluate splenic T cell and B cell subsets. The results showed that only the proportions of T helper 1 (Th1) and T helper 17 (Th17) cells exhibited significant differences, whereas no obvious changes were observed in B cells or regulatory T cells (Tregs).Salivary gland tissues were assessed by Hematoxylin-Eosin (HE) staining for inflammation and damage, and by immunofluorescence for Th1-epithelial cell co-localization.

AGO-treated mice showed significantly shorter immobility time in the tail suspension test versus untreated NOD controls, indicating reduced despair. AGO intervention also reduced splenic Th1 and Th17 cell proportions, alleviated salivary gland lymphocyte infiltration, and decreased Th1-epithelial cell co-localization, suggesting inhibition of Th1 cell migration to target tissues.

AGO significantly improved behavioral performance, reduced the proportion of Th1 cells in the spleen, and alleviated inflammatory infiltration in the salivary glands of NOD mice. These findings suggest that the drug may exert therapeutic effects by modulating immune responses and neurobehavioral functions, positioning it as a promising candidate for the treatment of SS.