title: Strain-dependent effects of the histamine H₄ receptor antagonist JNJ7777120 in a murine model of acute skin inflammation.
abstract: 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.
authors.affiliation: Department of Human Anatomy, Section of Pharmacology, University of Parma, Parma, Italy. gabriella.coruzzi@unipr.it
authors.forename: Gabriella
authors.initials: G
authors.lastname: Coruzzi
authors.forename: Cristina
authors.initials: C
authors.lastname: Pozzoli
authors.forename: Maristella
authors.initials: M
authors.lastname: Adami
authors.forename: Daniela
authors.initials: D
authors.lastname: Grandi
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Guido
authors.forename: Rogier
authors.initials: R
authors.lastname: Smits
authors.forename: Iwan
authors.initials: I
authors.lastname: de Esch
authors.forename: Rob
authors.initials: R
authors.lastname: Leurs
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003436:Croton Oil; D003872:Dermatitis / Q000188:drug therapy* / Q000473:pathology; D003879:Dermatologic Agents; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004431:Ear, External / Q000473:pathology; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011738:Pyrilamine / Q000627:therapeutic use; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4
chemical_list: D000893:Anti-Inflammatory Agents; D003879:Dermatologic Agents; D006634:Histamine H1 Antagonists; C498829:Hrh4 protein, mouse; D007211:Indoles; D010879:Piperazines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C484309:1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine; D003907:Dexamethasone; D003436:Croton Oil; D011738:Pyrilamine