Topical antihistamines enhance permeability barrier homeostasis and demonstrate efficacy in inflammatory dermatosis models

T. Lin, Mq. Man, Park K, Truus Roelandt, Y. Oda, M. Hupe, D. Crumrine, H. Lee, M. Gschwandtner, C. Trullas-Cabanas, E Tschachler, K. Feingold, P.m. Elias

Research output: Contribution to journalArticle

Abstract

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.Journal of Investigative Dermatology advance online publication, 27 September 2012; doi:10.1038/jid.2012.335.
Original languageEnglish
Pages (from-to)56-56
Number of pages1
JournalJournal of Investigative Dermatology
Volume132
Publication statusPublished - May 2012

Keywords

  • histamine antagonists
  • Dermatology
  • permeability
  • barrier function

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