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bioRxiv · 10.64898/2026.09.25.754340

Lactate Promotes an Anti-Inflammatory Phenotype in Activated Microglia

Omar Ibrahim, I.·Bouzier-Sore, A.-K.·Frezals, J.·Goudeneche, P.·Roumes, H.·Laroche-Traineau, J.
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Abstract

Microglial activation is a central component of neuroinflammatory responses in many brain pathologies. Increasing evidence indicates that microglial phenotype is tightly linked to cellular metabolism, with pro-inflammatory activation associated with enhanced glycolytic flux. Lactate, traditionally considered a metabolic substrate, has recently emerged as a signaling molecule capable of modulating immune responses. However, its direct impact on microglial inflammatory activation remains incompletely understood. In the present study, we investigated the effects of lactate on microglial phenotype under inflammatory conditions using primary rat microglial cultures stimulated with lipopolysaccharide (LPS). Microglial activation was assessed through the expression of phenotypic markers, cytokine production, and secreted chemokine profiles. LPS stimulation induced a strong pro-inflammatory response characterized by increased CD86 expression, elevated TNF-alpha secretion, and enhanced release of several pro-inflammatory chemokines. Post-treatment with sodium L-lactate significantly attenuated these inflammatory responses, reducing pro-inflammatory marker expression and cytokine secretion, while restoring the anti-inflammatory marker CD206. To explore the relevance of these findings in a pathological context, the effects of lactate were further examined in a neonatal rat model of hypoxia-ischemia. Sodium L-lactate administration after injury reduced microglial activation and promoted a shift toward an anti-inflammatory phenotype in cortical regions, whereas hippocampal microglia showed a more limited response. Together, these results demonstrate that lactate directly modulates microglial inflammatory activation and cytokine production in vitro and suggest that lactate-mediated metabolic signaling may contribute in vivo to the regulation of neuroinflammatory responses.

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Omar Ibrahim, I., Bouzier-Sore, A.-K., Frezals, J., Goudeneche, P., Roumes, H., Laroche-Traineau, J.. 2026-09-27. Lactate Promotes an Anti-Inflammatory Phenotype in Activated Microglia. https://doi.org/10.64898/2026.09.25.754340

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