Effect of different alcohols on stratum corneum kallikrein 5 and phospholipase A₂ together with epidermal keratinocytes and skin irritation

Abstract

OBJECTIVES:The aim of this exploratory study was to investigate the effect of ethanol, isopropanol and n-propanol on stratum corneum (SC) enzymes and keratinocytes in vitro together with their effects on skin condition and function. METHODS: Activities of kallikrein 5 (KLK5) and phospholipase A2 (PLA2) as well as keratinocyte metabolic activity, interleukin-1a (IL-1a) and tumor necrosis factor-a (TNF-a) were measured in vitro in the presence and absence of the different alcohols. We also measured transepidermal water loss (TEWL), skin capacitance, visual dryness and visual redness on the volar forearms of 25 Caucasian women following application of the alcohols 20 and 100 times per day over a period of 14 days in a clinical study. RESULTS: Reduced activities of KLK5 and PLA2 were observed in the presence of the alcohols. The greatest denaturing effect was always observed for n-propanol (P < 0.001), and in the case of PLA2, the effect of isopropanol was greater than ethanol (P < 0.001). Equally, ethanol had the mildest effects on keratinocyte metabolic activity and cytokine secretion (P < 0.001) and n-propanol always produced the most severe changes in normal and differentiated keratinocytes. These in vitro findings supported the clinical results where the major effects were on the induction of skin irritation (increased dropout rates) and ranked the intolerance of the different alcohols as follows: n-propanol > isopropanol > ethanol. At the high application frequencies, the effect of the different alcohols on transepidermal water loss (TEWL) and skin capacitance was similar, but at the low application frequencies, n-propanol had a significant effect on TEWL and capacitance values (P < 0.05). Equally, n-propanol and isopropanol produced significantly more skin redness at the low application frequencies. CONCLUSIONS: Clearly, isopropanol and n-propanol caused significant SC and keratinocyte perturbation in vitro together with damage to skin condition and function in vivo whereas ethanol did not. As a result, we show that ethanol-based sanitizers are better tolerated by skin, particularly in high-use settings, than other alcohols and should be the active ingredient of choice.R esum e OBJECTIFS: Le but de cette etude exploratoire etait d' etudier l'effet de l' ethanol, de l'isopropanol et du n-propanol sur les enzymes de la couche corn ee (SC) et les k eratinocytes in vitro ainsi que leurs effets sur l' etat de la peau et la fonction cutan ee. M ETHODES: Les activit es de la kallikr eine 5 (KLK5) et de la phospholipase A2 (PLA2), ainsi que l'activit e m etabolique des k eratinocytes, l'interleukine-1a (IL-1a) et le facteur de n ecrose tumorale-a (TNF) ont et e mesur es in vitro en pr esence et en l'absence des diff erents alcools. Nous avons egalement mesur e la perte d'eau trans epidermique (TEWL), la capacit e de la peau, la s echeresse visuelle et une rougeur visuelle sur les avant-bras palmaires de 25 femmes Caucasiennes apr es l'application des alcools 20 et 100 fois par jour sur une p eriode de 14 jou...

Barrier damaging effects of n‐propanol in occlusion‐modified tandem repeated irritation test: Modulation by exposure factors and atopic skin disease

“…The changes in the barrier function parameters after cumulative exposure to 60% n ‐propanol in a TRIT in healthy volunteers were initially studied by Kappes et al Using the same exposure model, we recently showed significant impairment of the permeability barrier function along with alterations of the corneocyte surface topography after exposure to the same concentration of the irritant and pointed to previously underestimated or unknown aspects of the irritant potential of short‐chain alcohols . Furthermore, the findings of the present and our previous studies are in agreement with observations of an earlier om‐TRIT study on the effects of 60% n ‐propanol and 0.5% SLS in the human skin in vivo as well as with the results of a recent controlled application test by Cartner et al, showing significant barrier function impairment after exposure to 70% n ‐propanol in healthy female volunteers . The pronounced irritant effect of n ‐propanol in vivo observed by Cartner et al was shown to translate in vitro to a marked cellular toxicity and significant tumor necrosis factor‐alpha (TNF‐α) release by the skin residential cell.…”

“…[22][23][24][25][26][27][28] Apart from these effects, short-chain alcohols, and in particular, n-propanol, were recently shown to reduce the activity of phospholipase A2 (PLA 2 ), one of the key enzymes involved in the maintenance of barrier homeostasis and lipid processing in the skin. 19 In an earlier publication, we provided first evidence for significant reduction in the stratum corneum NMF levels after om-TRIT with n-propanol and/or SLS and demonstrated that short-chain alcohols may cause skin dryness through interaction with both the skin lipids and reduction of NMF. 5 The results of the present study confirm and extend these observations by showing a significant decrease in the NMF levels after exposure to all tested n-propanol concentrations in both healthy and atopic skin.…”

“…Short‐chain alcohols are penetration enhancers and known to exert pronounced effects on the intercellular lipids, including disruption of the lipid lamellae, lipid phase transition, and alterations in the lipid organization . Apart from these effects, short‐chain alcohols, and in particular, n ‐propanol, were recently shown to reduce the activity of phospholipase A2 (PLA 2 ), one of the key enzymes involved in the maintenance of barrier homeostasis and lipid processing in the skin . In an earlier publication, we provided first evidence for significant reduction in the stratum corneum NMF levels after om‐TRIT with n ‐propanol and/or SLS and demonstrated that short‐chain alcohols may cause skin dryness through interaction with both the skin lipids and reduction of NMF .…”

Specific barrier response profiles after experimentally induced skin irritation in vivo

“…Elevated plasmin activity has previously been associated with a damaged skin barrier . Also, n‐propanol is known to induce changes in the SC; for example, it has pronounced denaturing effects on the SC proteins, profilaggrin processing, and desquamatory SC enzymes, which is consistent with marked decreases in skin capacitance and NMF levels, and changes in surface topography. A recent study showed the presence of another aliphatic alcohol, 2‐propanol, between the solid keratin rods inside the corneocytes, which might explain the morphological changes induced by n‐propanol in the present study .…”

The role of skin barrier in occupational contact dermatitis

“…The most frequently used alcohols are ethanol, iso‐ and n‐propanol. Although hand sanitizers seem to be less damaging for the skin barrier than soaps it has been demonstrated that they have the ability to induce changes in the SC; for example, n‐propanol has pronounced denaturing effects on the SC proteins, profilaggrin processing, and desquamatory SC enzymes . Consistently, Soltanipoor et al showed that n‐propanol caused remarkable changes in corneocyte surface topography and that this effect was strongly associated with a decrease in NMF and SC hydration.…”