Histamine: A mediator of inflammation.

Histamine and its receptors, including the recently discovered receptors (H(3) and H(4)), novel sources of histamine, and the place of histamine in mediator networks continue to be areas of great interest. The 4 major subtypes of histamine receptors, H(1) to H(4), differ in their location, second messengers, and histamine-binding characteristics. In addition, it would appear that different histamine receptor agonists and antagonists bind to different portions of the receptor complex. A fifth receptor subtype, the intracellular H(IC), has only been defined by its location within cell types that are not traditionally associated with histamine. In airway tissue, most cells express at least 1 subtype of histamine receptor; however, blockade of these receptors does not completely abolish the inflammatory response. In addition, some H(1)-antihistamines might also exert anti-inflammatory effects by pathways independent of H(1)-receptor binding. Studies of selected second-generation H(1)-antihistamines have shown that these agents inhibit the release of certain cytokines from basophils, acting at a point downstream from the calcium signaling pathway. It has not yet been determined whether this action represents a class effect.