Abstract | BACKGROUND:
Histamine is detected in high concentrations in the airways during an allergic asthma response. In a murine model of allergic asthma, JNJ 7777120, an antagonist at the histamine H(4) receptor, reduces asthmatic symptoms, while the histamine H(1) receptor-selective antagonist mepyramine is virtually without effect. In the present study, we analyzed the effect of combined antagonism at the histamine H(1) and H(4) receptors in a murine asthma model in relation to the timing of their application, i.e. sensitization or provocation. METHODOLOGY/PRINCIPAL FINDINGS: CONCLUSIONS/SIGNIFICANCE: Our study indicates that both histamine H(1) and H(4) receptors play important roles in the course of murine experimental asthma. Unexpectedly, the contribution of these receptors to the pathogenesis differs between the two phases, sensitization or provocation. Since in human asthma, repeated contact to the allergen is not only provocation but also a boost of sensitization, a combined pharmacological targeting of histamine H(1) and H(4) receptors could be taken into consideration as an option for the prevention of asthma and maybe other allergic diseases.
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Authors | Silke Beermann, Silke Glage, Danny Jonigk, Roland Seifert, Detlef Neumann |
Journal | PloS one
(PLoS One)
Vol. 7
Issue 1
Pg. e30285
( 2012)
ISSN: 1932-6203 [Electronic] United States |
PMID | 22272324
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cytokines
- Histamine Antagonists
- Histamine H2 Antagonists
- Hrh4 protein, mouse
- Indoles
- Piperazines
- Receptors, G-Protein-Coupled
- Receptors, Histamine
- Receptors, Histamine H4
- Immunoglobulin E
- 1-((5-chloro-1H-indol-2-yl)carbonyl)-4-methylpiperazine
- Ovalbumin
- Pyrilamine
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Topics |
- Animals
- Asthma
(drug therapy, immunology)
- Bronchial Hyperreactivity
(drug therapy, immunology)
- Bronchial Provocation Tests
- Bronchoalveolar Lavage Fluid
(cytology, immunology)
- Cytokines
(immunology, metabolism)
- Drug Administration Schedule
- Drug Therapy, Combination
- Enzyme-Linked Immunosorbent Assay
- Female
- Flow Cytometry
- Histamine Antagonists
(immunology, therapeutic use)
- Histamine H2 Antagonists
(immunology, therapeutic use)
- Humans
- Immunization
- Immunoglobulin E
(blood, immunology)
- Indoles
(immunology, therapeutic use)
- Mice
- Mice, Inbred BALB C
- Ovalbumin
(immunology)
- Piperazines
(immunology, therapeutic use)
- Pyrilamine
(immunology, therapeutic use)
- Receptors, G-Protein-Coupled
(immunology)
- Receptors, Histamine
(immunology)
- Receptors, Histamine H4
- Time Factors
- Treatment Outcome
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