Ketone metabolites of glycogen are produced as alternative cellular energy sources during periods of nutrient depravation or extreme exercise, processes that are associated with diminished innate immunity. In Nature Medicine, Dixit and colleagues report that the ketone β-hydroxybutyrate (BHB), which is produced by the liver during fasting, suppresses activation of the NLRP3 inflammasome in human monocytes. BHB, but not other four-carbon ketones or short-chain fatty acids, prevents the efflux of K+ ions and the formation of cytoplasmic adaptor ASC specks in response to ATP that functions as a 'signal 2' in the activation of NLRP3 after exposure to various inflammatory triggers. As a result, BHB blocks the generation and release of active IL-1β and IL-18. These findings help to explain how extreme caloric restriction acts to restrain innate immunity

Nat. Med. (16 February 2015) doi:10.1038/nm.3804