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February 2025

Fluoxetine promotes IL-10-dependent metabolic defenses to protect from sepsis-induced lethality
Gallant RM, Sanchez KK, Joulia E, Snyder JM, Metallo CM, Ayres JS. Fluoxetine promotes IL-10-dependent metabolic defenses to protect from sepsis-induced lethality. Sci Adv. 2025 Feb 14;11(7):eadu4034. doi: 10.1126/sciadv.adu4034. Epub 2025 Feb 14. PMID: 39951524; PMCID: PMC11827869.
  • SSRIs Overview: Among the most prescribed drugs globally, primarily used to enhance serotonergic signaling in the brain.
  • Beyond the Brain: SSRIs also impact immune and metabolic functions.
  • Infection Protection: Studies show SSRIs, including fluoxetine, protect against infections like sepsis and COVID-19, though mechanisms remain unclear.
  • Key Findings on Fluoxetine:Protection is independent of peripheral serotonin.
    • Increases circulating interleukin-10 (IL-10) levels.
    • IL-10 prevents sepsis-induced hypertriglyceridemia and associated cardiac issues (glucose oxidation impairment, lipid accumulation, ventricular stretch, potential cardiac failure).
  • Therapeutic Potential: Fluoxetine’s “off-target” effects offer a protective immunometabolic mechanism with possible clinical applications.