| Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function. | |
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MedLine Citation:
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PMID: 23014339 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Systemic antagonists of the histamine type 1 and 2 receptors (H1/2r) are widely used as anti-pruritics and central sedatives, but demonstrate only modest anti-inflammatory activity. Because many inflammatory dermatoses result from defects in cutaneous barrier function, and because keratinocytes express both Hr1 and Hr2, we hypothesized that H1/2r antagonists might be more effective if they were used topically to treat inflammatory dermatoses. Topical H1/2r antagonists additively enhanced permeability barrier homeostasis in normal mouse skin by the following mechanisms: (i) stimulation of epidermal differentiation, leading to thickened cornified envelopes; and (ii) enhanced epidermal lipid synthesis and secretion. As barrier homeostasis was enhanced to a comparable extent in mast cell-deficient mice, with no further improvement following application of topical H1/2r antagonists, H1/2r antagonists likely oppose mast cell-derived histamines. In four immunologically diverse, murine disease models, characterized by either inflammation alone (acute irritant contact dermatitis, acute allergic contact dermatitis) or by prominent barrier abnormalities (subacute allergic contact dermatitis, atopic dermatitis), topical H1/2r agonists aggravated, whereas H1/2r antagonists improved, inflammation and/or barrier function. The apparent ability of topical H1r/2r antagonists to target epidermal H1/2r could translate into increased efficacy in the treatment of inflammatory dermatoses, likely due to decreased inflammation and enhanced barrier function. These results could shift current paradigms of antihistamine utilization from a predominantly systemic to a topical approach. |
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Authors:
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Tzu-Kai Lin; Mao-Qiang Man; Juan-Luis Santiago; Kyungho Park; Truus Roelandt; Yuko Oda; Melanie Hupe; Debra Crumrine; Hae-Jin Lee; Maria Gschwandtner; Jacob P Thyssen; Carles Trullas; Erwin Tschachler; Kenneth R Feingold; Peter M Elias |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2012-09-27 |
Journal Detail:
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Title: The Journal of investigative dermatology Volume: 133 ISSN: 1523-1747 ISO Abbreviation: J. Invest. Dermatol. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-15 Completed Date: 2013-03-12 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 0426720 Medline TA: J Invest Dermatol Country: United States |
Other Details:
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Languages: eng Pagination: 469-78 Citation Subset: IM |
Affiliation:
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Dermatology Service, Department of Veterans Affairs Medical Center, and Department of Dermatology, UCSF, San Francisco, California 94121, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Administration, Topical Animals Cell Differentiation / drug effects, immunology Cimetidine / pharmacology Dermatitis, Atopic / drug therapy*, immunology* Dermatitis, Contact / drug therapy, immunology Diphenhydramine / pharmacology Disease Models, Animal Epidermis / drug effects*, immunology*, metabolism Female Histamine Antagonists / pharmacology* Histamine H1 Antagonists / pharmacology Histamine H2 Antagonists / pharmacology Homeostasis / drug effects, immunology Irritants / pharmacology Lipid Metabolism / drug effects, immunology Mice Mice, Hairless Permeability / drug effects |
| Grant Support | |
ID/Acronym/Agency:
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AR019098/AR/NIAMS NIH HHS; R01 AR019098/AR/NIAMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Histamine Antagonists; 0/Histamine H1 Antagonists; 0/Histamine H2 Antagonists; 0/Irritants; 51481-61-9/Cimetidine; 58-73-1/Diphenhydramine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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