An immune response study of oakmoss absolute and its constituents atranol and chloroatranol

Bonefeld, Charlotte M.; Nielsen, Morten Milek; Giménez‐Arnau, Elena; Lang, Matthieu; Vennegaard, Marie T.; Geisler, Carsten; Johansen, Jeanne Duus; Lepoittevin, Jean‐Pierre

doi:10.1111/cod.12177

Cited by 12 publications

(11 citation statements)

References 27 publications

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“…It was concluded by Kienhuis et al that the additive effect on the sensitization response when isoeugenol and cinnamal are mixed implies that quantitative risk assessment based on the response to single allergens in the products would be safe for the consumer (67). However, as we have shown that mice sensitized with mixtures of either HICC, cinnamal, isoeugenol or oak moss show an increased immune response upon challenge with either cinnamal or chloroatranol, respectively, as compared with that seen in mice sensitized only with the allergen used for challenge, in the same concentration as used in the mixture (70,71), we question this conclusion. There is no evidence that the levels identified in the current version of quantitative risk assessments based on LLNA results will be safe in the sense that no or few cases of sensitization will occur.…”

Section: The Effect On the Immune Responsementioning

confidence: 89%

“…Many individuals in the population are already sensitized to cinnamal and isoeugenol, and will not be protected. The mechanisms mediating the combination effect in elicitation are not fully known, but seem to be correlated with increased levels of danger signals, for example proinflammatory cytokines, during sensitization in mice exposed to the mixture as compared with those exposed to the single allergen (71). Taken together, these findings indicate that, for safety (hazard) evaluation of mixtures of allergens, the challenge response to single allergens within the mixture should be evaluated following sensitization with relevant mixtures.…”

Section: The Effect On the Immune Responsementioning

confidence: 99%

“…In addition to artificial fragrance allergens, several natural extracts exist, including the mixtures oak moss (Evernia prunastri) and tree moss (Evernia furfuracea). When we compared the immune response during sensitization induced by oak moss with the immune responses induced by two of the major identified allergens within oak moss, namely atranol and chloroatranol, we found that oak moss induced a much stronger response than that induced by either atranol or chloroatranol, as measured by both B cell infiltration and T cell proliferation in the dLNs (71). However, whether the increased response was mediated by a synergistic effect mediated by co-exposure to atranol and chloroatranol or by additional allergens in oak moss could not be determined in this experimental set-up (71).…”

Section: The Effect On the Immune Responsementioning

confidence: 99%

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Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

et al. 2017

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SummaryAllergic contact dermatitis is one of the most frequent forms of skin inflammation. Very often, we are exposed to mixtures of allergens with varying potencies, doses/areas, and exposure times. Therefore, improved knowledge about immune responses to combinations of contact allergens is highly relevant. In this article, we provide a general introduction to immune responses to contact allergens, and discuss the literature concerning immune responses to mixtures of allergens. According to the existing evidence, increased responses are induced following sensitization with combinations of allergens as compared with single allergens. The response to a mixture of allergens can be both additive and synergistic, depending on the dose and combination of allergens. Importantly, sensitization with combinations of either fragrance allergens or metal salts can result in increased challenge responses to specific allergens within the mixture. Taken together, the immune responses to mixtures of allergens are complex, and further studies are required to obtain the necessary knowledge to improve consumer safety.Key words: fragrances; hair dyes; metals; mixtures of allergens.Contact allergy is very frequent in the European population, as shown by Diepgen et al., who found that 27% were sensitised to common allergens (1). This may lead to allergic contact dermatitis if exposure exceeds the individual threshold of response.The allergic response is frequently directed towards nickel, cobalt, fragrances, hair dye chemicals, or preservatives. Many of these molecules are categorized as weak to moderate allergens -this term will be used throughout the article for (pre/pro)haptens (2). Surprisingly, even 'weak to moderate' allergens do induce allergic contact dermatitis in many people. This indicates that exposure parameters, such as dose and exposure frequency, are critical. Interestingly, consumers are rarely exposed to one isolated allergen, but are more often exposed to mixtures of allergens, for example in the form of metal alloys, cosmetics, and cleaning agents (3, 4). The impact of being exposed to a mixture of allergens instead of a single allergen has not been well studied. Studies from our group have suggested that exposure to mixtures of allergens has a great impact on the immune responses to single allergens within the mixture. In this review, we will discuss the current knowledge on how exposure to mixtures of contact allergens affects the immune system by (i) altering the chemical properties of single allergens in the mixtures, (ii) changing the inflammatory response, and (iii) affecting T cell activation, proliferation, and differentiation. Furthermore, we will discuss other factors, such as the presence of irritants, a disrupted skin barrier, local skin inflammation, and local skin memory, that could increase the response to allergens. Finally, we will discuss the clinical impact of

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Section: The Effect On the Immune Responsementioning

confidence: 89%

Section: The Effect On the Immune Responsementioning

confidence: 99%

Section: The Effect On the Immune Responsementioning

confidence: 99%

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Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

et al. 2017

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“…The draining lymph nodes (LN) were harvested, and single-cell suspensions were prepared for FACS analysis and stained for CD8 expression and BrdU incorporation as previously described [31]. The left ears were individually homogenized in a Precellys 24 tissue homogenizer (Bertin Technologies, Montigny-le-Bretonneux, France), and total RNA was extracted with a RNeasy kit (Qiagen, Hilden,Germany) as previously described [32]. The samples were DNase treated and RNA concentrations were measured using a Nanodrop 2000 C Spectrophotometer (Thermo Scientific, Roskilde, Denmark).…”

Section: Transwell Migrationmentioning

confidence: 99%

Midline 1 controls polarization and migration of murine cytotoxic T cells

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Hansen

Nielsen

et al. 2014

Immunity Inflam & Disease

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Midline 1 (MID1) is a microtubule-associated ubiquitin ligase that regulates protein phosphatase 2 A levels. Loss-of-function mutations in MID1 lead to the human X-linked Opitz G/BBB (OS) syndrome characterized by defective midline development during embryogenesis. We have recently shown that MID1 is strongly up-regulated in murine cytotoxic T lymphocytes (CTLs), and that it has a significant impact on exocytosis of lytic granules and the killing capacity of CTLs. The aims of the present study were to determine the localization of MID1 in migrating CTLs, and to investigate whether MID1 affects CTL polarization and migration. We found that MID1 mainly localizes to the uropod of migrating CTLs and that it has a substantial impact on CTL polarization and migration in vitro. Furthermore, analysis of contact hypersensitivity responses supported that MID1 controls effector functions of CTLs in hapten-challenged skin in vivo. These results provide significant new knowledge on the role of MID1 in CTL biology.

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“…A stronger challenge response to cinnamaldehyde was observed in mice sensitized with the mixture than in mice sensitized with cinnamaldehyde alone. We conducted similar studies with atranol and chloroatranol, main allergens of oak moss absolute, showing that the mixture in the natural extract was more potent at both sensitization and challenge than atranol and chloroatranol alone . These findings suggested that allergen mixtures could enhance both induction and elicitation of ACD.…”

Section: Introductionmentioning

confidence: 99%

Is it possible to assess the allergenicity of mixtures based on in chemico methods? Preliminary results on common fragrance aldehydes

Lang

Giménez‐Arnau

Lepoittevin

2016

Flavour & Fragrance J

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Most perfume compositions and cosmetics contain mixtures of fragrance ingredients, synthetic or extracted from natural sources. Many of these are known to be weak or moderate allergens when tested individually. However, fragrances are one of the most common causes of allergic contact dermatitis to consumer products, ranking second after nickel. As consumers are exposed to mixtures of ingredients when using products that contain perfume, it was suggested that mixtures could enhance induction and elicitation of skin allergy to fragrances. Prediction of skin sensitization to chemicals is crucial for the cosmetics industry. Nowadays, methods to assess skin sensitization hazard replacing the use of animals have been developed and validated for the testing of pure substances. However, there is practically no experience with testing of mixtures. Here we evaluated in a very preliminary approach, and from a chemical reactivity perspective, if the validated DPRA, hapten‐peptide reactivity based assay, could be used at a first sight to evaluate the chemical reactivity of mixtures. Two simple binary combinations of fragrance aldehydes were studied, hydroxycitronellal‐citral and citral‐cinnamaldehyde. Their reactivity towards DPRA peptides was compared with that of the single constituents. In general, the chemical described as the most potent sensitizer was driving the reactivity in the mixtures. Therefore, it could be hypothesized that the DPRA would estimate the mixture chemical reactivity similar to that of the stronger sensitizer component. This will be reinforced by conditions described for the DPRA where the tested chemical or mixture of chemicals will be added in large excess to the peptides. Copyright © 2016 John Wiley & Sons, Ltd.

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An immune response study of oakmoss absolute and its constituents atranol and chloroatranol

Abstract: Atranol and chloroatranol can elicit both sensitization and challenge reactions, but the mixture of allergens in oakmoss absolute is more potent than atranol and chloroatranol alone.

Cited by 12 publications

References 27 publications

Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

Immunological, chemical and clinical aspects of exposure to mixtures of contact allergens

Midline 1 controls polarization and migration of murine cytotoxic T cells

Is it possible to assess the allergenicity of mixtures based on in chemico methods? Preliminary results on common fragrance aldehydes

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