Premium
Strain‐dependent effects of the histamine H 4 receptor antagonist JNJ7777120 in a murine model of acute skin inflammation
Author(s) -
Coruzzi Gabriella,
Pozzoli Cristina,
Adami Maristella,
Grandi Daniela,
Guido Nicoletta,
Smits Rogier,
de Esch Iwan,
Leurs Rob
Publication year - 2012
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.1600-0625.2011.01396.x
Subject(s) - croton oil , histamine , pharmacology , histamine receptor , inflammation , pyrilamine , histamine h1 receptor , histamine h4 receptor , antagonist , croton , mast cell , receptor antagonist , dexamethasone , receptor , histamine h1 antagonists , thioperamide , medicine , histamine h2 receptor , cimetidine , immunology , traditional medicine
The effects of the histamine H 4 receptor antagonist JNJ7777120 were evaluated in a model of acute skin inflammation induced by local application of croton oil. The influence of strain on the effect of JNJ7777120 was investigated in four different mouse strains (CD‐1, NMRI, BALB/c and C57BL/6J). In CD‐1 mice, JNJ777720 (30–100 mg/kg subcutaneously, s.c.) exerted a dose‐dependent inhibition of croton oil‐induced ear inflammation and polymorphonuclear leucocyte infiltration, as confirmed by histological evaluation of ear tissues. JNJ7777120 (30–100 mg/kg) did not reduce ear oedema in NMRI, BALB/c or C57BL/6J mice. The positive control, dexamethasone (2 mg/kg s.c.) induced significant anti‐inflammatory effects only in CD‐1 and NMRI mice. In these strains, also the histamine H 1 ‐receptor blocker pyrilamine (30 mg/kg s.c.) significantly reduced ear oedema at 2 h after croton oil challenge, being as effective as JNJ7777120 in CD‐1 mice. Taken together, these data demonstrate that the H 4 receptor antagonist JNJ7777120 may reduce acute croton oil‐induced skin inflammation as effectively as H 1 receptor blockade. However, present experiments evidenced for the first time marked strain‐related differences in the JNJ7777120 pharmacological activity, which have to be carefully considered when using this ligand to characterize histamine H 4 receptor functions in murine models and translating preclinical data to clinical human settings.