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Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function.

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.

SUBMITTER: Lin TK

PROVIDER: S-EPMC3532566 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function.

Lin Tzu-Kai TK Man Mao-Qiang MQ Santiago Juan-Luis JL Park Kyungho K Roelandt Truus T Oda Yuko Y Hupe Melanie M Crumrine Debra D Lee Hae-Jin HJ Gschwandtner Maria M Thyssen Jacob P JP Trullas Carles C Tschachler Erwin E Feingold Kenneth R KR Elias Peter M PM

The Journal of investigative dermatology 20120927 2

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 permeab ...[more]

PMID: 23014339

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Project description:IntroductionThe pathogenesis of seborrheic dermatitis (SD) is multifactorial and traditional treatments may not target all aspects of it. The aim of this study was to evaluate short-term anti-fungal, anti-microbial, anti-inflammatory and anti-pruritus properties of a novel non-steroidal cream (NSC) containing piroctone olamine, zinc salt of L-pyrrolidone carboxylate (PCA), hydroxyphenyl propamidobenzoic acid, biosaccharide gum-2 and stearyl glycyrrhetinate in patients with face and chest SD.MethodsTwelve male subjects affected by SD, presenting face and chest manifestations, were enrolled. Patients were instructed to apply NSC twice a day, performing regular visits at baseline (W0), after 7 (W1) and 14 (W2) days of treatment. A limitation of the study was that no control group treated with the vehicle without active ingredients was enrolled. To evaluate the efficacy of the NSC, investigator's assessments were represented by scoring index (SI) and investigator's global assessment score (IGA). In order to assess NSC anti-fungal and anti-microbial effects, skin scale scrapings were collected and used for Malassezia furfur (MF) and Staphylococcus epidermidis (SE) cultures. In parallel, in order to assess NSC anti-inflammatory effects, gene expression of IL-1α, IL-1β, IL-6, IL-8, and TNF-α was assessed. In addition, anti-pruritus effects were also evaluated through gene expression of cathepsin S and L-histidine decarboxylase.ResultsSI mean scores significantly decreased at W1 and, to a greater extent, at W2 compared with W0. The IGA score registered an important improvement efficacy both for face and chest, from W1 to W2. MF and SE growth was already inhibited at W1, with a more pronounced decrease at W2. Gene expression of all analyzed mediators was significantly reduced at W1 compared to W0.ConclusionIn conclusion, our assessment is that NSC is an effective and well tolerated treatment option for SD with anti-fungal, anti-microbial and anti-inflammatory properties.Trial registrationISRCTN registry, ISRCTN77871064 (retrospectively registered October 17, 2019). EudraCT number, 2019-003813-32.FundingISDIN.

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Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function.

Publications

Topical antihistamines display potent anti-inflammatory activity linked in part to enhanced permeability barrier function.

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