Ketone bodies inhibit mast cell degradation and protect against anaphylaxis

Ketone bodies play critical roles in organismal energy homeostasis; however, their effects on various diseases remain unknown. We investigated the effects of two ketone bodies, β-hydroxybutyric acid (β-HB) and acetoacetic acid (AcAc), on type I hypersensitivity in vitro and in vivo. The effects of β-HB and AcAc on mast cell degradation, as monitored by β-hexosaminidase release in rat basophilic leukemia RBL-2H3 cells, and hypothermic anaphylaxis, a potentially deadly allergic reaction, were evaluated in an anaphylactic mouse model. Both β-HB and AcAc inhibited β-hexosaminidase release from RBL-2H3 cells in a concentration-dependent manner. The inhibitory effects of AcAc were greater than those of β-HB. The inhibitory effects of β-HB and AcAc were significantly attenuated in the presence of a GPR109A receptor antagonist mepenzolate bromide and GPR43A antagonist GLPG0974. β-HB and AcAc did not affect the viability of RBL-2H3 cells at concentrations below 100 µmol/L. In an anaphylactic mouse model, the intraperitoneal injection of AcAc (1 µmol/mouse) inhibited anaphylactic hypothermia, whereas the injection of β-HB (1–10 µmol/mouse) did not. These results suggest that β-HB and AcAc, especially AcAc, are effective in type I hypersensitivity reactions, such as anaphylaxis, by inhibiting mast cell degradation. [Display omitted] •Ketone bodies are composed of β-HB, AcAc, and acetone.•Both β-HB and AcAc inhibited mast cell degradation in vitro.•AcAc inhibited anaphylactic hypothermia in mice.•AcAc may be effective in type I hypersensitivity reactions, such as anaphylaxis.