The role of histamine H-1 and H-4 receptors in allergic inflammation: The search for new antihistamines

Histamine has a key role in allergic inflammatory conditions. The inflammatory responses resulting from the liberation of histamine have long been thought to be mediated by the histamine H-1 receptor, and H-1-receptor antagonists-commonly known as antihistamines-have been used to treat allergies for many years. However, the importance of histamine in the pathology of conditions such as asthma and chronic pruritus may have been underestimated. Here, we review accumulating evidence suggesting that histamine indeed has roles in inflammation and immune function modulation in such diseases. In particular, the discovery of a fourth histamine receptor (H-4) and its expression on numerous immune and inflammatory cells has prompted a re-evaluation of the actions of histamine, suggesting a new potential for H-4-receptor antagonists and a possible synergy between H-1 and H-4-receptor antagonists in targeting various inflammatory conditions.