Summary of
β-Hydroxybutyrate Suppresses NLRP3 Inflammasome–Mediated Inflammatory Disease
By
Purpose
To determine whether BHB directly inhibits the NLRP3 inflammasome and thereby reduces inflammation across disease models.
Methods
Researchers used LPS-primed mouse macrophages and in vivo models of peritonitis, urate crystal inflammation, and familial cold autoinflammatory syndrome (FCAS). BHB was administered systemically or added to cultures, and inflammasome activation (via IL-1β release and ASC speck formation) was measured.
Results
BHB dose-dependently suppressed IL-1β secretion and blocked NLRP3 activation across multiple inflammatory triggers (ATP, nigericin, urate crystals). The effect was independent of glycolysis, ROS inhibition, or histone deacetylase activity. In vivo, BHB reduced inflammation in peritonitis and crystal-induced models. In FCAS mice, BHB-fed animals showed lower IL-1β levels and less systemic inflammation.
Conclusion
BHB acts as an endogenous inhibitor of the NLRP3 inflammasome, revealing a novel anti-inflammatory mechanism independent of calorie restriction or fasting. This supports therapeutic use of ketones for metabolic and neuroinflammatory diseases.
