The histamine H₄ receptor: targeting inflammatory disorders

Eur J Pharmacol. 2011 Oct 1;668(1-2):1-5. doi: 10.1016/j.ejphar.2011.06.029. Epub 2011 Jul 3.


The discovery of the histamine H(4) receptor has added a new chapter to the century of extensive biogenic amine research. The human histamine H(4) receptor is mainly expressed in cells of the human immune system (e.g. mast cells, eosinophils, monocytes, dendritic cells, T cells) and mediates several effects on chemotaxis with numerous cell types. The distinct expression pattern and the immunomodulatory role highlight its physiological relevance in inflammatory and immunological processes. Inflammatory conditions, e.g. allergy, asthma and autoimmune diseases, were for a long time thought to be mainly mediated by activation of the histamine H(1) receptor subtype. However, in the treatment of diseases as chronic pruritus, asthma and allergic rhinitis the use of histamine H(1) receptor antagonists is unsatisfying. Selective H(4) receptor ligands and/or synergism of histamine H(1) and H(4) receptor modulation may be more effective in such pathophysiological conditions. Promising preclinical studies underline its role as an attractive target in the treatment of inflammatory and autoimmune disorders. Meanwhile, first histamine H(4) receptor antagonist has reached clinical phases for the treatment of respiratory diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism*
  • Inflammation / pathology
  • Molecular Targeted Therapy / methods*
  • Protein Transport
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Histamine / chemistry
  • Receptors, Histamine / genetics
  • Receptors, Histamine / metabolism*
  • Receptors, Histamine H4
  • Signal Transduction


  • HRH4 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H4