[Frontiers in Bioscience S3, 985-994, June 1, 2011]

Pathogenetic and therapeutic implications of the histamine H4 receptor in inflammatory skin diseases and pruritus

Ralf Gutzmer1, Maria Gschwandtner1, Kristine Rossbach2, Susanne Mommert1, Thomas Werfel1, Manfred Kietzmann2, Wolfgang Baeumer2

1 Hannover Medical School, Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Ricklinger Str. 5, D-30449 Hannover, Germany , 2 University of Veterinary Medicine, Institute for Pharmacology, Toxicology and Pharmacy, Bünteweg 17, D-30559 Hannover, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
2. Introduction
3. Expression and function of the H4R on relevant cell types
3.1. APC
3.2. T-cells
3.3. Natural Killer cells
3.4. Granulocytes
3.5. Skin cells (Keratinocytes, Fibroblasts, Mast cells)
4. Animal models
5. Pruritus and H4R expression on nerve cells
6. Summary
7. Acknowledgements
8. References

1. ABSTRACT

Chronic inflammatory skin diseases such as atopic dermatitis (AD) are clinically characterized by erythematous and pruritic skin lesions, immunologically mediated by an inflammatory infiltrate consisting of T-cells, antigen presenting cells (APC) and eosinophilic granulocytes. Histamine levels are increased in lesions of inflammatory skin diseases. It is likely that histamine also plays a pathogenetic role since various relevant cell types such as T-cells and APC express functional histamine receptors. However, therapeutic blockade of the histamine H1 and H2 receptor is inefficient at least in the treatment of atopic dermatitis. We summarize here current data on the role of the recently described histamine H4 receptor (H4R) in chronic inflammatory skin diseases. The H4R is functionally expressed on relevant cell types such as T-cells, APC and keratinocytes. In murine models of contact hypersensitivity and pruritus, H4R blockade had significant in vivo effects. Taken together, several lines of evidence suggest a role of the H4R in chronic inflammatory skin disease and the H4R might be a therapeutic target for diseases such as AD.