Histamine: A mediator of inflammation

Histamine and its receptors, including the recently discovered receptors (H₃ and H₄), 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, H₁ to H₄, 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_1C, 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 H₁-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 down-stream from the calcium signaling pathway. It has not yet been determined whether this action represents a class effect.