Comparison of the effect of glycerol and triamcinolone acetonide on cumulative skin irritation in a randomized trial.

BACKGROUND: So-called anti-irritants are added to cosmetic formulations because of their alleged beneficial effect on irritated skin. Documentation for these claims is often limited. However, glycerol has shown anti-irritant properties in experimentally induced irritation from sodium lauryl sulfate and nonanoic acid (NON). This study was designed to further substantiate that glycerol added to cosmetic formulations has an anti-irritant effect on experimentally induced skin irritation. OBJECTIVE: We sought to compare glycerol with triamcinolone acetonide as treatments for cutaneous irritation in human volunteers. METHODS: Irritation was induced by 3 daily arm washes for a week with 10% sodium lauryl sulfate on one arm and 30% NON on the other. To maintain irritation, for the next 12 days volunteers washed their arms twice daily with the irritants. Treatments were applied immediately after washing. The treatments (including vehicle and no treatment) were randomized to sites using a Latin square design. The reactions were evaluated clinically and instrumentally. LIMITATIONS: Study was designed to only detect potent anti-irritants. CONCLUSION: Glycerol reduced the irritant effect of both sodium lauryl sulfate and NON, whereas triamcinolone acetonide appeared to have beneficial effect only on the irritation induced by NON. The study provided experimental documentation for the claim that glycerol has anti-irritant effect in a cosmetic formulation.

Psoriasiform skin disease in transgenic pigs with high-copy ectopic expression of human integrins α2 and ß1.

Psoriasis is a complex human-specific disease characterized by perturbed keratinocyte proliferation and a pro-inflammatory environment in the skin. Porcine skin architecture and immunity are very similar to that in humans, rendering the pig a suitable animal model for studying the biology and treatment of psoriasis. Expression of integrins, which is normally confined to the basal layer of the epidermis, is maintained in suprabasal keratinocytes in psoriatic skin, modulating proliferation and differentiation as well as leukocyte infiltration. Here, we generated minipigs co-expressing integrins α2 and ß1 in suprabasal epidermal layers. Integrin-transgenic minipigs born into the project displayed skin phenotypes that correlated with the number of inserted transgenes. Molecular analyses were in good concordance with histological observations of psoriatic hallmarks, including hypogranulosis and T-lymphocyte infiltration. These findings mark the first creation of minipigs with a psoriasiform phenotype resembling human psoriasis and demonstrate that integrin signaling plays a key role in psoriasis pathology.

Induced keratinocyte hyper-proliferation in alpha2beta1 integrin transgenic mice results in systemic immune cell activation.

alpha2beta1 integrins are normally confined to the proliferating basal layers of the epidermis. However, during wound healing and in psoriasis, these integrins are expressed on keratinocytes in suprabasal layers correlating with a less differentiated phenotype. Transgenic mice expressing alpha2beta1 integrins under the involucrine promoter have previously been demonstrated, to various degrees, spontaneously develop a skin disorder resembling psoriasis. Herein, we show that a mild epidermal wounding induces a uniform acanthosis together with an influx of immune cells. The disease initiates as a normal wound healing process and is completely restored in wildtype mice by day 14. However, in the integrin transgenic mice a chronic inflammation develops, a process that can be compared to the Koebner phenomenon in psoriatic patients. In this study, we have followed the integrin transgenic mice for five weeks, where substantial keratinocyte hyper-proliferation, inflammatory infiltration and high cytokine levels within the skin can still be observed. In addition, draining lymph nodes were dramatically increased in size and contained highly activated T cells, as well as APCs secreting large amounts of pro-inflammatory cytokines. Furthermore, the systemic immune response was affected with increased spleen size, elevated cytokine levels in the serum and altered lymphocyte trafficking patterns, very much resembling what is seen in psoriasis patients. Finally, CD4(+) T cell depletion was not able to affect the onset or progression of skin inflammation. This suggests that altered keratinocyte differentiation and proliferation can drive a skin inflammation and cause chronic immune cell activation both at a local and systemic level.

Anti-irritants II: Efficacy against cumulative irritation.

So-called anti-irritants (AI) are widely used in cosmetic formulations, with the aim of reducing irritation from substances in the formulation. It may also be claimed that they are 'soothing' and 'healing' ingredients. However, the proof for these claims is circumstantial. The dose-response effect of 4 alleged AI (nifedipine, (-)-alpha-bisabolol, canola oil and glycerol) was studied on experimentally induced acute irritation in healthy volunteers, and only glycerol showed dose-related response and effects potentially better than no treatment. The acute irritation model only allowed a small window of opportunity in which to demonstrate efficacy. Therefore, the effect of AI was studied in a cumulative irritation model by inducing irritant dermatitis with 10 min daily exposures for 5+4 days (no irritation on weekend) to 1% sodium lauryl sulfate on the right and 20% nonanoic acid on the left volar forearm. AI ointments were applied twice daily. Clinical scoring was performed daily, evaporimetry (Trans Epidermal Water Loss), hydration and colourimetry were measured at baseline (D0), in the middle and at the end of treatment. The glycerol ointment was the only treatment statistically better than both 'no treatment' and vehicle.

Anti-irritants I: Dose-response in acute irritation.

The term 'anti-irritant' (AI) was coined in 1965 by Goldemberg to describe a diverse group of topical product ingredients, which were able to reduce the irritation potential of other more irritating ingredients in the same product. 'AIs' are being added to cosmetic formulations in order, allegedly, to benefit tolerability of the products and allow claims such as 'soothing' and 'healing' ingredients. Limited documentation in favour of the efficacy of AIs is published. We studied the dose-related effect of 4 alleged AIs (nifedipine, (-)-alpha-bisabolol, canola oil and glycerol) on experimentally induced acute irritation in healthy volunteers. Each AI was used in 3 concentrations. Acute irritation was induced by occlusive tests with 1% sodium lauryl sulfate and 20% nonanoic acid in N-propanol. The irritant reactions were treated twice daily with AI-containing formulations from the time of removal of the patches. Evaluation of skin irritation and efficacy of treatments were performed daily for 4 days using clinical scoring, evaporimetry (transepidermal water loss), hydration measurement and colourimetry. Only glycerol showed dose-response and effects potentially better than no treatment. There was no significant effect and no difference between the three other AIs.