Histamine in idiopathic inflammatory bowel diseases--not a standby player

In inflamed bowel there is sustained local secretion of histamine not only from activated mast cells but also from some infiltrating cells. Released histamine acting through different receptors may exert variety of effects. H1 receptors mediate inflammatory effects i.e. smooth muscle and endothelial cell contractions, increased vascular permeability, but also antibody production; H2 and H4 receptors are involved in modulation of cytokine production and various immunomodulatory effects including eosinophil and mast cell chemotaxis and calcium influx in these cells, neutrophil chemotaxis, which affect inflammatory responses. Thus many, if not all events that are triggered by histamine could in consequence contribute to the severity of disease. Accordingly, elicited by histamine shift of Thl/Th2 towards Th2 potentiates inflammatory changes and makes the tissue more prone to some infections and tumors, normally eliminated by Thl dependent mechanisms. Preferential H4 receptor location on immune cells and recently reported anti-inflammatory effect of its highly specific antagonist administered in vivo in mouse model of peritonitis, suggest that the question of whether H4 antagonists will be used as anti-inflammatory drugs in human clinic will soon get an answer.