Aims: 

To explore functions of histamine beyond its well established classic inflammatory mediator effects.

Methods: 

Histamine- and histamine receptor deficient knockout mice contributed substantially to unfold the immunoregulatory roles of histamine far beyond its inflammatory effects.

Results: 

Data obtained by other groups and our laboratory indicated several non-immune effects exerted e.g. on benign and malignant cell proliferation. Furthermore, it was shown that histamine modulates maturation, antigen uptake and migration of dendritic cells, and alters their antigen presentation and T cell polarizing capacity. Histamine inhibits TH1, induces TH2 cells, and influences the antibody isotype distribution. According to our results, in histidine decarboxylase knockout mice the genetic lack of histamine affects myeloid ontogeny (e.g. that of osteoclasts and eosinophils), it causes alteration of autoantibody patterns, increases DNFB hypersensitivity, enhances survival after C. pneumoniae infection, alters cytokine production by the placenta, provides protection against DSS-induced colitis, results in reduced haptoglobin and IL-6 production and increases the production of both IFN g and NO. In the background of the highly diverse immunoregulatory effects of histamine, there is signalization through the four known types of histamine receptors. Our data, obtained using the H4 histamine receptor knockout mice, suggest that histamine exerts its effects on dendritic cell antigen presentation, migration and cytokine production via the H4 histamine receptor.

Conclusion: 

These findings indicate that the recently discovered H4 histamine receptor plays a distinguished role in the immunoregulatory functions of histamine.