Lessons from Glucocorticoids, Metformin, and Dimethyl Fumarate: Could Targeting Immunometabolism Lead to Better Anti-Inflammatory Therapies?

Résumé fourni par la source

Emerging evidence suggests that alterations in immunometabolism contribute to pathogenesis of inflammatory diseases, providing potential therapeutic targets. Anti-inflammatory drugs such as glucocorticoids, metformin, and dimethyl fumarate (DMF) modulate key immunometabolic pathways. Glucocorticoids boost itaconate production, which exerts anti-inflammatory effects via multiple targets, including by modification of cysteines on inflammatory proteins. Metformin, known for inhibiting gluconeogenesis in type 2 diabetes, also blocks mitochondrial Complex I and increases GDF-15, a regulator of food intake with anti-inflammatory properties, which may explain effects of metformin on inflammation. DMF, like itaconate, modifies cysteines on target proteins, notably KEAP1, leading to Nrf2 activation, which induces antioxidant enzymes and suppresses inflammatory gene expression. These immunometabolic actions suggest that targeting immune cell metabolism could provide new strategies for treating autoimmune diseases. This review explores recent advances in itaconate, GDF-15, and Nrf2 signaling and how harnessing these pathways may lead to novel anti-inflammatory therapies for patients with inflammatory diseases.

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