Skin Treatment with Detergent Induces Dermatitis with H1-Antihistamine-Refractory Itch and Upregulates IL-4 and Th17/Th22 Cytokine Gene Expression in C57BL/6 Mice

Abstract

<b><i>Introduction:</i></b> Repeated skin contact to detergents causes chronic irritant contact dermatitis (ICD) associated with itch sensation and eczema. However, the mechanisms of detergent-induced ICD are poorly understood. Here, we established a new murine model of detergent-induced ICD with H1-antihistamine-refractory itch. <b><i>Methods:</i></b> Ear skin of wild-type and mast cell-deficient mice on the C57BL/6 genetic background was treated with a detergent, sodium dodecyl/lauryl sulfate (SDS), daily for approximately 2 weeks with or without administration of an H1-antihistamine, fexofenadine. Skin inflammation, barrier dysfunction, and itching were analyzed. Quantitative PCR for earlobe gene expression and flow cytometry analysis for draining lymph node cells were conducted. <b><i>Results:</i></b> SDS treatment induced skin inflammation with ear swelling, increased transepidermal water loss, and hind-paw scratching behaviors in the wild-type and mast cell-deficient mice. The peak value of scratching bouts was retained for at least 48 h after the last SDS treatment. H1-antihistamine administration showed no or little reduction in the responses. SDS treatment upregulated gene expression for a Th2 cytokine IL-4 and Th17/Th22 cytokines, IL-17A, IL-17F, and IL-22, and increased cell numbers in draining lymph nodes of CD4<sup>+</sup> T, CD8<sup>+</sup> T, and γδT cells with enhanced expression of GATA3, RORγt, T-bet, or FOXP3 compared with untreated mice. <b><i>Conclusions:</i></b> The present study showed that SDS treatment of ear skin in C57BL/6 mice induces mast cell-independent skin inflammation with H1-antihistamine-refractory itch and suggested a possible Th cytokine- and/or lymphocyte-mediated regulation of the model. The model would be useful for elucidation of mechanisms for inflammation with H1-antihistamine-refractory itch in detergent-induced ICD.

Physical influences on the skin barrier and pathogenesis of allergy

“…Nonatopic healthcare workers had a significant TEWL increase after hand sanitizer use compared with nonatopic nonhealthcare workers ( P < 0.05), suggesting that healthcare workers have a compromised skin barrier from frequent hand hygiene. In mice, exposure to the cytotoxic ingredients in detergents caused increase in pro-inflammatory cytokines with increased TEWL [73 ▪ ] and skin inflammation with itch and upregulation of cytokines involved in allergic responses [74 ▪ ,75 ▪ ].…”

Jonzac Thermal Spring Water Reinforces Skin Barrier Function of Human Skin and Presents a Soothing and Regenerating Effect

“…Interesting, very recently, Masutani and collaborators showed that detergents including sodium dodecyl sulphate induce mast cell-independent skin inflammation with H1-antihistamine-refractory itch in mouse skin [16].…”