Inducible histamine protects mice from hepatitis through H ₂-receptor stimulation

Histamine is well known for its roles in allergic diseases and anaphylaxis through H₁-receptor stimulation. The H₁-receptor stimulation by histamine results in an increase in vascular permeability, vasodilatation, and stimulation of nerve terminals in primary sensory neurons, thereby accelerating the inflammatory responses. On the other hand, histamine has been demonstrated to be involved in the regulation of innate and acquired immune responses through H₂-receptors. In a previous study with human peripheral blood mononuclear cells, we observed that histamine exerts various regulatory effects on monocyte/macrophage function. In this review, we discuss how inducible histamine protects mice from lethal hepatitis, induced by heat-killed P.acnes (1 mg, i.v.) followed by challenge with a low dose of lipopolysaccharide (1 mg), by reducing the excessive cytokine response in the liver. In addition, from in vivo studies with histidine decarboxylase knockout and H₁-, H₂-receptor knockout mice, the protective effect of histamine against fulminant hepatitis is shown to be elicited through H ₂-receptor stimulation.