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Respiratory Research

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Open Access 01-12-2010 | Research

Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines

Authors: Jeffery M Cowden, Jason P Riley, Jing Ying Ma, Robin L Thurmond, Paul J Dunford

Published in: Respiratory Research | Issue 1/2010

Abstract

Background

Airway remodeling and dysfunction are characteristic features of asthma thought to be caused by aberrant production of Th2 cytokines. Histamine H₄ receptor (H₄R) perturbation has previously been shown to modify acute inflammation and Th2 cytokine production in a murine model of asthma. We examined the ability of H₄R antagonists to therapeutically modify the effects of Th2 cytokine production such as goblet cell hyperplasia (GCH), and collagen deposition in a sub-chronic model of asthma. In addition, effects on Th2 mediated lung dysfunction were also determined.

Methods

Mice were sensitized to ovalbumin (OVA) followed by repeated airway challenge with OVA. After inflammation was established mice were dosed with the H₄R antagonist, JNJ 7777120, or anti-IL-13 antibody for comparison. Airway hyperreactivity (AHR) was measured, lungs lavaged and tissues collected for analysis.

Results

Therapeutic H₄R antagonism inhibited T cell infiltration in to the lung and decreased Th2 cytokines IL-13 and IL-5. IL-13 dependent remodeling parameters such as GCH and lung collagen were reduced. Intervention with H₄R antagonist also improved measures of central and peripheral airway dysfunction.

Conclusions

These data demonstrate that therapeutic H₄R antagonism can significantly ameliorate allergen induced, Th2 cytokine driven pathologies such as lung remodeling and airway dysfunction. The ability of H₄R antagonists to affect these key manifestations of asthma suggests their potential as novel human therapeutics.

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Title: Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines
Authors: Jeffery M Cowden
Jason P Riley
Jing Ying Ma
Robin L Thurmond
Paul J Dunford
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2010
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/1465-9921-11-86

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Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines

Abstract

Background

Methods

Results

Conclusions

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Abstract

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