Histamine in allergic inflammation and immune modulation

Histamine, originally considered as a mediator of acute inflammatory and immediate hypersensitivity responses has also been demonstrated to affect chronic inflammation and regulate several essential events in the immune response. On the other hand, various cytokines control histamine synthesis, release and expression of histamine receptors (HRs). The cells involved in the regulation of immune response and hematopoiesis express HRs and also secrete histamine, which can selectively recruit the major effector cells into tissue sites and affect their maturation, activation, polarization and effector functions leading to chronic inflammation. Histamine, acting through its receptor type 2, positively interferes with the peripheral antigen tolerance induced by T regulatory cells in several pathways. Histamine also regulates antigen-specific Th1 and Th2 cells, as well as related antibody isotype responses. The diverse effects of histamine on immune regulation are due to differential expression and regulation of four HRs and their distinct intracellular signals. In addition, differences in affinities of these receptors are highly decisive on the biological effects of histamine and agents that target HRs. This article highlights the findings leading to a change of perspective in histamine immunobiology.