Histamine: The Quintessential Mediator

Histamine is unique in being the only substance described to date which fulfils all of the criteria established by Dale for an inflammatory mediator. Thus, histamine is known to cause the "Triple Response" of Lewis and to act via H1 and H2 receptors to produce vasodilation and increased vascular permeability; elevated levels of histamine are found in inflamed tissue; histamine is produced and stored in mast cells and there are established mechanisms for histamine release via mast cell surface receptors; and antihistamines alleviate the clinical manifestations of histamine release. There have been several recent advances in our understanding of histamine pharmacology and of the pathomechanisms of chronic idiopathic urticaria (CIU), a disease in which histamine plays an important role. Two new histamine receptors have been identified, the inhibitory (H3) receptor and the intracellular (H(ic)) receptor involved in cell proliferation. There is now evidence that mast cell derived histamine release in patients with CIU is due to an autoimmune disease, mediated by autoantibodies to the alpha-subunit of the high affinity IgE receptor on mast cells and basophils. Removal of these autoantibodies by plasmapheresis, or treatment with intravenous immunoglobulins may cause clinical remission. Cyclosporin A has also been found to be of benefit to some patients with CIU probably due to a mast cell "stabilising" effect, leading to reduced release of histamine and other mediators. This article reviews our current knowledge on histamine, its role, receptors and mechanisms for release.