Effects of impermeable and semipermeable glove materials on resolution of inflammation and epidermal barrier impairment after experimental skin irritation.

BACKGROUND: Semipermeable membranes might be suitable for glove liners or comfort gloves in individuals with irritant contact dermatitis (ICD). OBJECTIVES: To evaluate the effects of different glove materials on inflammation and epidermal barrier impairment after experimental skin irritation. METHODS: Nine test areas on the volar forearms of 24 healthy volunteers were irritated with sodium lauryl sulfate (1%) and afterward covered for 6 days (6 or 8 h/day) with semipermeable Sympatex (SYM), vinyl (OCC), combinations of vinyl with Sympatex (SYM/OCC) or cotton (COT/OCC), or left uncovered (CON). Up to day 10, measurements of transepidermal water loss (TEWL), erythema (a*), skin humidity (SH) and visual scoring (VS) were applied. RESULTS: No significant differences in skin parameters were found between COT/OCC and SYM/OCC as well as between each of the combinations and CON. SYM, COT/OCC and SYM/OCC led to better results for most skin parameters than OCC alone. CONCLUSIONS: Occlusive material has a negative impact on skin barrier recovery and inflammation after skin irritation whereas SYM is not inferior to uncovered areas indicating good tolerability. Altogether, the data suggest that SYM is a useful alternative to COT as material for glove liners and comfort gloves in ICD patients.

CCL2‒CCR2 Signaling in the Skin Drives Surfactant-Induced Irritant Contact Dermatitis through IL-1ß‒Mediated Neutrophil Accumulation.

Surfactant-induced cumulative irritant contact dermatitis (ICD) is a common and clinically important skin disorder. CCL2 is known to mediate inflammation after tissue damage in various organs. Thus, we investigated whether and how CCL2 contributes to the development of murine cumulative ICD induced by a common surfactant, SDS. Wild-type mice treated topically with SDS for 6 consecutive days developed skin inflammation that recapitulated the features of human cumulative ICD, including barrier disruption, epidermal thickening, and neutrophil accumulation. CCL2 was upregulated in SDS-treated skin, and local CCL2 blockade attenuated SDS-induced ICD. SDS-induced ICD and neutrophil accumulation were also attenuated in mice deficient in CCR2, the receptor for CCL2. Neutrophil depletion alleviated SDS-induced ICD, suggesting that impaired neutrophil accumulation was responsible for the amelioration of ICD in CCR2-deficient mice. In RNA-sequencing analyses of SDS-treated skin, the expression levels of Il1b in Ccr2-deficient mice were highly downregulated compared with those in wild-type mice. Furthermore, the intradermal administration of IL-1ß in the SDS-treated skin of CCR2-deficient mice restored the local accumulation of neutrophils and the development of ICD. Collectively, our results suggest that CCL2‒CCR2 signaling in the skin critically promotes the development of SDS-induced ICD by inducing IL-1ß expression for neutrophil accumulation.

Effects of constant light exposure on allergic and irritant contact dermatitis in mice reared under constant light conditions.

Environmental light levels can affect physiological functions, such as general activity, body temperature and metabolism. Irregular lifestyles, such as those involving exposure to light during the night, can exacerbate the clinical symptoms of several inflammatory skin diseases. However, the effects of constant light exposure on immune responses are not fully understood. This study aimed to elucidate the effects of constant light exposure on two major types of skin reactions, allergic contact dermatitis (ACD) and irritant contact dermatitis (ICD). BALB/c mice were kept under constant light conditions or a normal light and dark cycle, and their ACD and ICD responses were assessed after the topical application of 2,4,6-trinitro-1-chlorobenzene and croton oil, respectively, to the ear skin. Interestingly, in both ACD and ICD, the ear-swelling response and local leukocyte infiltration were aggravated by constant exposure to light, which has previously been shown to severely disturb the behavioural rhythms of mice. In ACD, these findings were accompanied by increases in the numbers of degranulated mast cells and eosinophils. These results suggest that constant light exposure intensifies allergic and non-allergic skin inflammation.

Elevated Skin pH Is Associated With an Increased Permeability to Synthetic Urine.

PURPOSE: The aim of this study was to investigate the permeability of the skin following cleansing activities and its susceptibility to synthetic urine penetration. SUBJECTS AND SETTING: Ten healthy volunteers (aged 22-58 years) participated in the study, which was conducted in a university bioengineering laboratory. METHODS: Tape stripping and sodium lauryl sulfate were used to simulate the physical and chemical irritation exacerbated by frequent cleansing activities, respectively. An untreated site also was selected to evaluate responses of intact skin. Synthetic urine was then applied for a period of 2 hours. Measurements of transepidermal water loss and skin pH were taken at baseline and after each challenge. To quantify the permeability of the skin following exposure, desorption curves of transepidermal water loss were measured and skin surface water loss was calculated. RESULTS: Chemically irritated skin, characterized by increased pH (7.34 ± 0.22), demonstrated an increased permeability to urine, as reflected by a significant increase in mean skin surface water loss (46,209 ± 15,596 g/m2) compared to both the intact (14,631 ± 6164 g/m2) and physically irritated (14,545 ± 4051 g/m2) skin (P = .005 in both cases). In contrast, the differences between the intact and physically irritated skin were not significant (P = .88). CONCLUSION: Permeability of the skin to irritants is influenced by the status of the skin and its acid mantle. These highlight the need to reevaluate the frequency of cleansing activities, along with the choice of product in clinical settings, favoring the use of pH-balanced cleansers.

Stratum corneum levels of inflammatory mediators and natural moisturizing factor in patch test reactions to thiurams and fragrances and their possible role in discrimination between irritant and allergic reactions to hapten mixtures.

BACKGROUND: Patch test (PT) reactions to thiuram mix (TM) and fragrance mix (FM) I or II without concomitant reactions to their single constituents are potentially caused by the irritant properties of the mixes. OBJECTIVE: Comparing inflammatory profiles of PT reactions to TM, FM I, FM II, and their constituents and assessing their potential in discrimination of irritant and allergic reactions. PATIENTS AND METHODS: Levels of 14 cytokines and natural moisturizing factor (NMF) were determined in stratum corneum samples collected from PT reactions to TM, FM I or II, their constituents, and petrolatum (pet.) control sites in 36 individuals. RESULTS: Levels of interleukin (IL)-16, chemokine (CXC motif) ligand (CXCL) 8, CXCL10, chemokine (CC motif) ligand (CCL) 17, and CCL22 were significantly increased in reactions (+, ++) to thiurams and fragrances compared to their petrolatum. controls, except for PT reactions to FM I/II with negative breakdown testing in which, however, decreased levels of NMF were observed. In doubtful reactions to FM I/II with negative breakdown testing, NMF was significantly lower than in petrolatum controls. CONCLUSIONS: PT reactions to thiurams and fragrances indicate a Th2-skewed inflammation. The inflammatory profiles suggest that weak or doubtful FM I/II reactions without accompanying reaction to a constituent were irritant. IL-16 might be suitable to distinguish irritant from allergic reaction.

Oleic acid exhibits an expressive anti-inflammatory effect in croton oil-induced irritant contact dermatitis without the occurrence of toxicological effects in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cutaneous inflammatory diseases, such as irritant contact dermatitis, are usually treated with topical corticosteroids, which cause systemic and local adverse effects limiting their use. Thus, the discovery of new therapeutic alternatives able to effectively treat skin inflammatory disorders, without causing adverse effects, is urgently needed. AIM OF THE STUDY: To investigate the topical anti-inflammatory effect of oleic acid (OA), a monounsaturated fatty acid, into Pemulen® TR2-based semisolid dosage forms, employing a croton oil-induced irritant contact dermatitis model in mice. MATERIALS AND METHODS: Male Swiss mice were submitted to skin inflammation protocols by acute and repeated applications of croton oil. The anti-inflammatory activity of Pemulen® TR2 hydrogels containing OA was evaluated by assessing oedema, inflammatory cell infiltration, and pro-inflammatory cytokine IL-1ß levels. The mechanisms of action of OA were evaluated using cytokine IL-1ß application or pretreatment with the glucocorticoid antagonist mifepristone. Possible toxic effects of OA were also assessed. RESULTS: Pemulen® TR2 3% OA inhibited the acute ear oedema [maximal inhibition (Imax) = 76.41 ± 5.69%], similarly to dexamethasone (Imax = 84.94 ± 2.16%), and also inhibited ear oedema after repeated croton oil application with Imax = 85.75 ± 3.08%, similar to dexamethasone (Imax = 81.03 ± 4.66%) on the day 7 of the experiment. Croton oil increased myeloperoxidase activity, which was inhibited by Pemulen® TR2 3% OA (Imax = 71.37 ± 10.97%) and by 0.5% dexamethasone (Imax = 96.31 ± 3.73%). Pemulen® TR2 3% OA also prevented the increase in pro-inflammatory cytokine IL-1ß levels induced by croton oil (Imax = 94.18 ± 12.03%), similar to 0.5% dexamethasone (Imax = 87.21 ± 10.58%). Besides, both Pemulen® TR2 3% OA and 0.5% dexamethasone inhibited IL-1ß-induced ear oedema with an Imax of 80.58 ± 2.45% and 77.46 ± 1.92%, respectively. OA and dexamethasone anti-inflammatory effects were prevented by 100% and 91.43 ± 5.43%, respectively, after pretreatment with mifepristone. No adverse effects were related to Pemulen® TR2 3% OA administration. CONCLUSIONS: OA demonstrated anti-inflammatory efficacy similar to dexamethasone, clinically used to treat skin inflammatory conditions, without presenting adverse effects.

CD44 expression in human skin: High expression in irritant and allergic contact dermatitis and moderate expression in psoriasis lesions in comparison with healthy controls.

BACKGROUND: Previous research using animal models demonstrated that CD44 expression may contribute to directing inflammatory cells into skin lesions during inflammation development in allergic contact dermatitis (ACD). OBJECTIVES: To examine CD44 expression in patients with ACD and irritant contact dermatitis (ICD), and to compare it to patients with psoriatic lesions and healthy controls' (HCs) skin. METHODS: This study included 200 patients comprising four groups of 50 each: ACD, ICD, psoriasis vulgaris, and HCs. CD44 expression was determined by immunohistochemical analysis using an optical microscope, and the results were visualized semiquantitatively by determining the percentage of immunoreactive cells in the epidermis, dermis, and on lymphocytes. RESULTS: The highest CD44 expression was found in ICD, followed by ACD, psoriasis vulgaris, and lastly, the HCs (P < .001). Epidermal CD44 expression was significantly higher in contact dermatoses (especially in ICD) compared with psoriasis and healthy skin (P < .001). Similarly, CD44 expression in the dermis and on lymphocytes was strongest in ICD, although less pronounced than in the epidermis. CONCLUSIONS: Because significantly elevated CD44 expression in ICD might be related to its function in maintaining and preserving the skin barrier in affected patients, further research on disease pathogenesis and new treatment options is needed.

Skin Delivery and Irritation Potential of Phenmetrazine as a Candidate Transdermal Formulation for Repurposed Indications.

Phenmetrazine, a selective dopamine and norepinephrine releaser, previously available as an oral anorectic, is prone to be abused. This study aimed to assess the feasibility of delivering phenmetrazine via the transdermal route for a new indication, while also minimizing its abuse potential. The passive permeation of phenmetrazine through dermatomed human cadaver skin was evaluated using static Franz diffusion cells at 10 mg/mL for the fumarate salt, and at 20, 40, and 80 mg/mL for the free base in propylene glycol for 24 h. Further, oleic acid (5% w/w), oleyl alcohol (5% and 10% w/w), and lauric acid (10% w/w) were investigated as chemical permeation enhancers to enhance the delivery. Skin irritation potential was assessed using EpiDerm™ in vitro reconstructed human epidermal model. The free base showed superior 24-h delivery (8.13 ± 4.07%, 10.6 ± 2.5%, and 10.4 ± 1.4% for groups with 20, 40, and 80 mg/mL of the free base, respectively) to phenmetrazine fumarate salt (undetectable). The successful screening of effective chemical enhancers, oleyl alcohol (5% and 10% w/w), oleic acid (5% w/w), and lauric acid (10% w/w) resulted in significant enhancement of delivery. The calculated therapeutic relevant flux for the potential indication, attention deficit hyperactivity disorder, 20 µg/cm2/h was met, where a 24-mg daily dose from a 50-cm2 patch was projected to be delivered to a 60-kg individual. Irritation study results suggest that formulations with therapeutically relevant delivery are likely to be non-irritant. In conclusion, it is feasible to deliver therapeutically relevant amounts of phenmetrazine via the transdermal route.

The Unique Molecular Signatures of Contact Dermatitis and Implications for Treatment.

Irritant contact dermatitis (ICD) and allergic contact dermatitis (ACD) are common skin disorders that are characterized by inflammation, oozing, crusting, and pruritus. Atopic dermatitis (AD) is an inflammatory skin disease characterized by immune and barrier abnormalities and is additionally a risk factor for acquiring ICD and ACD. New work on allergic sensitization to common allergens (e.g., nickel and fragrance) in human skin has shown that different allergens have distinct molecular fingerprinting. For example, nickel promotes strong Th1/Th17 polarization, whereas fragrance allergy causes Th2/Th22 skewing, which is similar to the phenotype of AD. While ACD has previously been considered to be constant across all allergens, largely based on mouse models involving strong sensitizers, these new data suggest that ACD differs mechanistically according to allergen. Further, ACD in the setting of concurrent AD shows a different and attenuated phenotype as compared to healthy individuals with ACD, which influences the way AD patients respond to vaccination and other treatment modalities. As in contact sensitization, skin challenged by food patch testing shows that common food allergens (e.g., peanut and barley) also cause distinct immune polarizations in the skin. Additionally, house dust mite reactions in human skin have been profiled to show unique Th2, Th9, and Th17/22 activation as compared to controls, which are similar to the phenotype of psoriasis and contact responses to nickel. Given this information, ACD patients should be treated based on their unique allergen polarity. Refined understanding of the molecular behavior of contact dermatitis and related diseases translates to improved methods of inducing tolerance in sensitized allergic patients, such as with targeted drug therapy and epicutaneous immunotherapy.

Defensive Effects of a Unique Polysaccharide, Sacran, to Protect Keratinocytes against Extracellular Stimuli and Its Possible Mechanism of Action.

Sacran, a polysaccharide isolated from the alga Aphanothece sacrum (Suizenji-nori), has unique physical and physiological characteristics. In a previous study, we reported that sacran improves skin conditions in individuals who suffer from atopic dermatitis (AD), focusing on its trapping function against extrinsic stimuli compared with hyaluronic acid (HA). First, we examined the penetration of sacran through stratum corneum (SC) with an impaired barrier function using immature reconstructed human epidermal equivalents. Sacran penetrates the SC to living cell layers of the epidermis, which suggested that sacran would attenuate adverse influences in keratinocytes caused by extracellular factors such as irritants or proinflammatory cytokines such as interleukin 1α (IL-1α). Sacran markedly reduced the cell damage induced by a nonionic detergent, sodium lauryl sulfate (SLS). Moreover, sacran restored the elevation of intracellular reactive oxygen species (ROS) levels stimulated by SLS and by IL-1α. These effects of sacran were superior to those of HA. In order to investigate the restoration effects of sacran, the influence of sacran on the physical properties of lipid bilayers was evaluated by measuring the order parameter using the ESR spin-labeling method. Because sacran failed to cause changes in the order parameters of liposomes and HaCaT keratinocytes, these results indicate that sacran does not interact with lipid bilayers although it restored changes in the order parameter caused by SLS. The sum of these results demonstrates that sacran reduces the influence of extracellular stimuli by its trapping effects. We conclude that the improving action of sacran is based on its trapping effect.

Specific barrier response profiles after experimentally induced skin irritation in vivo.

BACKGROUND: Recently, natural moisturizing factors (NMFs) and corneocyte surface topography were suggested as biomarkers for irritant dermatitis. OBJECTIVES: To investigate how exposure to different irritants influences corneocyte surface topography, NMF levels and the barrier function of human skin in vivo. METHODS: Eight healthy adult volunteers were exposed to aqueous solutions of 60% n-propanol, 0.5% sodium lauryl sulfate (SLS), 0.15% sodium hydroxide, and 2.0% acetic acid, and distilled water, in a repeated irritation test over a period of 96 hours. Erythema, transepidermal water loss (TEWL), skin hydration, the dermal texture index (DTI) and NMF levels were measured at baseline, and after 24 and 96 hours. RESULTS: SLS and sodium hydroxide had the most pronounced effects on erythema and TEWL. Although n-propanol caused only slight changes in TEWL and erythema, it showed pronounced effects on skin hydration, NMF levels, and the DTI. NMF was the only parameter that was significantly altered by all investigated irritants. The changes in the DTI were inversely associated with NMF levels and skin hydration. CONCLUSION: Skin barrier impairment and the inflammatory response are irritant-specific, emphasizing the need for a multiparametric approach to the study of skin irritation. NMF levels seem to be the most sensitive parameter in detecting irritant-induced skin barrier alterations.

Topical ROR Inverse Agonists Suppress Inflammation in Mouse Models of Atopic Dermatitis and Acute Irritant Dermatitis.

The retinoic acid receptor-related orphan receptors RORα and RORγ are critical for the functions of specific subsets of T cells and innate lymphoid cells, which are key drivers of inflammatory disease in barrier tissues. Here, we investigate the anti-inflammatory potential of SR1001, a synthetic RORα/γ inverse agonist, in mouse models of atopic dermatitis and acute irritant dermatitis. Topical treatment with SR1001 reduces epidermal and dermal features of MC903-induced atopic dermatitis-like disease and suppresses the production of type 2 cytokines and other inflammatory mediators in lesional skin. In the epidermis, SR1001 treatment blocks MC903-induced expression of TSLP and reverses impaired keratinocyte differentiation. SR1001 is also effective in alleviating acute dermatitis triggered by 12-O-tetradecanoylphorbol-13-acetate. Overall, our results suggest that RORα/γ are important therapeutic targets for cutaneous inflammation and suggest topical usage of inhibitory ligands as an approach to treating skin diseases of inflammatory etiology.

Stratum corneum profiles of inflammatory mediators in patch test reactions to common contact allergens and sodium lauryl sulfate.

BACKGROUND: Recent studies have demonstrated allergen-specific differences in the gene expression of inflammatory mediators in patch tested skin. OBJECTIVES: To determine levels of various inflammatory mediators in the stratum corneum (SC) after patch testing with common contact allergens and the skin irritant sodium lauryl sulfate (SLS). METHODS: In total, 27 individuals who had previously patch tested positive to nickel, chromium, methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) or para-phenylenediamine were retested and then patch tested with SLS and petrolatum, with petrolatum serving as the patch test control. At 72 h, the test sites were clinically graded and the SC samples collected on adhesive tape. RESULTS: The levels of 18 of the 32 quantified mediators differed significantly from that of the control patches for at least one of the tested substances. SLS and MCI/MI induced the largest number of immunomediators. Interleukin (IL)-16 levels were significantly higher in patch test reactions in all allergens than they were in the controls, while no significant difference was detected for SLS. Furthermore, a strong negative correlation was found between strength of patch test reaction and IL-1α levels. CONCLUSIONS: Cytokine profiles in the SC of patch tested skin did not show a distinct allergen-specific pattern. However, MCI/MI induced a larger and wider immune response than the other allergens, perhaps due to its potency as an irritant. The levels of IL-16 were significantly increased in patch test reactions to allergens but not to SLS; thus, they may help clinicians to differentiate between allergic contact dermatitis and irritant contact dermatitis.

In vivo skin penetration of macromolecules in irritant contact dermatitis.

Recently, a selective preferential accumulation of polymeric nanoparticles (in the size range around 100nm) has been observed in the follicular system of dermatitis skin. The present investigation aimed at clearly investigating the effect of irritant contact dermatitis on the barrier permeability for colloidal systems below this size range, namely quantum dots and hydrophilic macromolecules. Irritant dermatitis was induced in mice and the penetrability of quantum dots (5nm) and hydrophilic dextran molecules has been tracked in both healthy and inflamed skin using confocal laser scanning microscopy. The selective accumulation of the quantum dots was clearly observed in inflamed skin while hydrophilic dextran behaved similarly in both healthy and inflamed skin. The therapeutic potential for the transdermal delivery of peptide drugs through inflamed skin has been also tested in rats. Results revealed that the transdermal permeation of insulin and calcitonin was not significantly enhanced in dermatitis compared to healthy skin. On the other side, permeation through stripped skin was significantly higher. However, the effect was limited and shorter compared to the SC injection where tmin was 0.5h and 2h with a 70% and 46% reduction in blood glucose levels for the stripped skin and the SC injection respectively. Similarly, tmin was 4h and 8h with area under the curve of 161±65% and 350±97% for the stripped skin and the SC injection respectively. In conclusion, the changes in skin permeability accompanied with skin inflammation did not affect its permeability to peptide drugs. Our findings also underline that experiments with the tape stripped skin model as a surrogate for inflamed skin can risk misleading conclusions due to significant difference of skin permeability between the tape stripped skin and inflamed skin.

Human sebum extract induces barrier disruption and cytokine expression in murine epidermis.

BACKGROUND: Previous studies have shown that human sebum may play a role in barrier function but with much debate. OBJECTIVE: To elucidate the effects of human sebum on skin barrier function. METHODS: We used hairless mouse skin to study the functional and morphological alternation of epidermis after the application of human sebum. RESULTS: The results showed a significant increase in transepidermal water loss and erythema value, and a decrease in skin hydration, accompanied by epidermal hyperplasia with parakeratosis following sebum application. Nile red staining together with electron microscopic examination confirmed the underlying mechanisms for sebum-induced barrier disruption are related directly to the interaction of sebum with the intracellular lipid lamellae of the SC, thereby leading to the increase in the fluidity of SC intracellular lipids as demonstrated by ATR-FTIR measurement. An inflammatory reaction characterized by an enhanced cytokine cascade, including up-regulation of TNF-α, IL-1α and IL-6, was also observed. On the other hand, there were insignificant expression of thymic stromal lymphopoietin and unchanged serum levels of IgE, suggesting non-immunogenic stimulation by sebum treatment. CONCLUSION: It may be concluded that inflammation induced by excess amount of sebum is more likely an irritant contact dermatitis rather than an allergic one. Moreover, these findings implicated possible relationships between sebum, irritant contact dermatitis, and seborrheic dermatitis.

Skin barrier integrity and natural moisturising factor levels after cumulative dermal exposure to alkaline agents in atopic dermatitis.

Dermal exposure to alkaline agents may lead to skin barrier damage and irritant contact dermatitis. The objective of this study was to investigate the effects of cumulative exposure to 0.5% sodium lauryl sulphate (SLS) and 0.15% NaOH on the barrier function and natural moisturising factor (NMF) levels in atopic dermatitis and healthy volunteers with known filaggrin genotype. The skin response was monitored by measurement of erythema and transepidermal water loss. The stratum corneum NMF levels were determined by high-performance liquid chromatography. Repeated exposure to 0.5% SLS and/or 0.15% NaOH in atopic dermatitis resulted in more severe impairment of the skin barrier function. Cumulative exposure to the irritants reduced significantly NMF in both the atopic and healthy controls group. The pronounced decrease of NMF after repeated single and sequential irritant exposure may be a pathogenetically relevant factor for development of chronic irritant contact dermatitis in both healthy and atopic individuals.

[The changes of skin barrier of patients with different facial dermatitis and the comparison of CE and KLK5].

OBJECTIVE: To study the clinical symptoms and the condition of skin barrier of different facial dermatitis. METHODS: The patients with facial dermatitis were divided into 4 groups based on their diagnosis: hormone-dependent dermatitis (HDD) group, sensitive skin (SS) group, cosmetic intolerance (CI) group and normal control group. All patients received the evaluation on clinical symptoms with measuring scale, measurements of stratum corneum water content (SCWC), sebum, pH, trans-epidermal water loss (TEWL) and blood flow. The skin scales were collected for the measurements of the ratio of immature cornified envelope (CE) via immunofluorescence and the concentration of kallikrein 5 (KLK5) via enzyme-linked immunosorbent assay. RESULTS: There were total 146 patients included (HDD 38, SS 53, CI 15, control group 30), most of them had their symptoms evaluated as moderate to severe. Compared with the control, the disease groups had lower SCWC and sebum (P < 0.05), higher pH, TEWL and blood flow (P < 0.05), higher ratio of immature CE (P = 0.011) and lower concentration of KLK5 (P = 0.000); while these parameters among the disease groups did not show statistical significant difference. CONCLUSION: There is no difference in the clinical symptoms and the condition of skin barrier between facial dermatitis with different inducements. The growth of CE may be inhibited and the concentration of KLK5 decreases in facial dermatitis.

Oral administration of glucosylceramide ameliorates inflammatory dry-skin condition in chronic oxazolone-induced irritant contact dermatitis in the mouse ear.

BACKGROUND: Irritant contact dermatitis (ICD) is an inflammatory skin disease triggered by exposure to a chemical that is toxic or irritating to the skin. A major characteristic of chronic ICD is an inflammatory dry-skin condition with associated itching. Although glucosylceramide (GlcCer) is known to improve the skin barrier function, its mechanism of action is unknown. OBJECTIVES: Using a mouse model of oxazolone-induced chronic ICD, this study investigated the effects of oral administration of GlcCer on inflammatory dry skin. METHODS: Chronic ICD was induced by repeated application of oxazolone in mice. GlcCer was orally administered once daily throughout the elicitation phase. The beneficial efficacy of GlcCer on cutaneous inflammation was evaluated by assessing ear thickness, lymph node weight, histological findings, and mRNA expression of pro-inflammatory cytokines such as IL-1ß and IL-6. Additionally, parameters of the itch-associated response, including scratching behavior, water content of the skin, and aquaporin-3 levels in the lesional ear, were measured. RESULTS: Oral GlcCer administration significantly suppressed mRNA expression of the pro-inflammatory cytokines IL-1ß and IL-6. GlcCer also suppressed ear swelling, lymph node weight gains, and infiltration of leukocytes and mast cells in ICD mice. In oxazolone-induced ICD mice, GlcCer significantly inhibited irritant-related scratching behavior and dehydration of the stratum corneum, and decreased aquaporin-3 expression. CONCLUSIONS: Our results indicate that GlcCer suppressed inflammation not only by inhibiting cytokine production but also by repairing the skin barrier function, suggesting a potential beneficial role for GlcCer in the improvement of chronic ICD.