Publikationsdatenbank

Role of the histamine H1, H2 and H4 receptor in a mouse model of chronic dermatitis (2023)

Art

Poster

Autoren

Vidak, J. (WE 14)

Filor, V. (WE 14)

Singto, T. (WE 14)

Bäumer, W. (WE 14)

Kongress

15th International Congress of the European Association for Veterinary Pharmacology and Toxicology

Bruges, Belgium, 02. – 05.07.2023

Quelle

Journal of veterinary pharmacology and therapeutics

Bandzählung: 46

Heftzählung: S1

Seiten: 128

ISSN: 1365-2885

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/epdf/10.1111/jvp.13368

DOI: 10.1111/jvp.13368

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Introduction:
Activation of histamine H4 receptors is important in the development and progression of atopic dermatitis (AD). Histamine H4 receptor antagonists can reduce inflammation, improve epidermal barrier function, clinical symptoms and reduce pruritus intensity. The toluene diisocyanate (TDI) mouse model is a frequently used model to study AD, as it replicates skin lesions and pruritus as observed in human and canine patients with AD.

Material and Methods:
In the first experiment, the TDI model was performed in H4R-Knockout (H4R KO) mice. Inflammation and itch intensity were compared between normal wild type (WT) and H4R KO mice by applying TDI to one mouse ear and back skin in five separate challenges. Inflammatory reactions were measured based on changes in ear thickness. We also conducted a second study with the same TDI model in H4R KO mice: This trial used both olopatadine, a H1 receptor antagonist, and the H2 receptor agonist amthamine. Additionally, both drugs were combined in one group. As a comparator, we included two vehicle (PBS) groups (WT and H4R KO). All substances were injected subcutaneously 1 h before and 12 h after TDI application.

Results:
After the three successive challenges in the first study, H4R KO mice showed much lower inflammatory responses than WT mice. Pruritus increased after the initial three challenges in both WT and H4R KO mice. However, no discernible differences were found between WT and H4R KO animals regarding their itch behavior. Unexpectedly, in the second study, there was no difference in inflammation between the groups. However, an impressive change in pruritus intensity was seen: the H4R KO vehicle group showed the highest scratching frequency, followed by those given amthamine and olopatadine. The scratching behavior was further reduced in H4R KO mice that received the combination of amthamine and olopatadine. An unexpected result was that the WT vehicle group scratched far less than any other group in this experiment.

Conclusions:
One possible explanation for the reduced WT reaction is, that these WT mice had been bought from a vendor in the second experiment, whereas for the first experiment colony bred WT mice have been used. To bolster these conclusions, further analysis of the data like calcium imaging of dorsal root ganglia (DRG) are currently performed. These findings imply that the H4 receptor is involved in allergy associated chronic inflammation and itch. However, data are prone to some variability that make final conclusions difficult.