The histamine H4 receptor: A novel modulator of inflammatory and immune disorders

All 4 known histamine receptors (H1R, H2R, H3R and H4R) have been used or proposed as therapeutic targets for varied diseases. This article reviews the recent progress in understanding the function of the recently described histamine receptor H4R in a variety of immune responses and the potential therapeutic value of H4R antagonists. The H4R is expressed primarily on cells involved in inflammation and immune response. It has effects on chemotaxis, as well as cytokine and chemokine production of mast cells, eosinophils, dendritic cells, and T cells. H4R antagonists, JNJ 7777120 and JNJ 10191584 (also known as VUF 6002) have been developed with excellent affinity and selectivity towards human and rodent H4R. These antagonists also demonstrate efficacy as anti-inflammatory agents in vivo. H4R antagonists have shown promising activity in down-regulating immune responses in a range of animal disease models including acute inflammation, hapten-mediated colitis, and allergic airway inflammation. Due to its distribution on immune cells and its proven role in inflammatory functions, the H4R appears to be a therapeutic target for the treatment of a variety of immune disorders.