RESUMEN
Previously, we found that astaxanthin (AST) elicited an anti-inflammatory response in an experimental atopic dermatitis (AD) model. However, the use of AST was limited because of low bioavailability and solubility. We hypothesized that liposome formulation of AST could improve this. In this study, we compared the anti-inflammatory and anti-dermatotic effects of liposomal AST (L-AST) and free AST. We evaluated the effect of L-AST on a phthalic anhydride (PA)-induced animal model of AD by analyzing morphological and histopathological changes. We measured the mRNA levels of AD-related cytokines in skin tissue and immunoglobulin E concentrations in the serum. Oxidative stress and transcriptional activities of signal transducer and activator of transcription 3 (STAT3) and nuclear factor (NF)-κB were analyzed via western blotting and enzyme-linked immunosorbent assay. PA-induced dermatitis severity, epidermal thickening, and infiltration of mast cells in skin tissues were ameliorated by L-AST treatment. L-AST suppressed AD-related inflammatory mediators and the inflammation markers, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 in PA-induced skin conditions. Oxidative stress and expression of antioxidant proteins, glutathione peroxidase-1 (GPx-1) and heme oxygenase-1 (HO-1), were recovered by L-AST treatment in skin tissues from PA-induced mice. L-AST treatment reduced transcriptional activity of STAT3 and NF-κB in PA-induced skin tissues. Our results indicate that L-AST could be more effective than free AST for AD therapy.
Asunto(s)
Antiinflamatorios/administración & dosificación , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/tratamiento farmacológico , Anhídridos Ftálicos/efectos adversos , Animales , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Sistemas de Liberación de Medicamentos/métodos , Liposomas , Masculino , Ratones , Ratones Pelados , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Piel/inmunología , Piel/patología , Resultado del Tratamiento , Xantófilas/administración & dosificaciónRESUMEN
The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 6 trimellitic anhydride copolymers as used in cosmetics. These ingredients are related as copolymers in that they all share trimellitic anhydride (ie, 1,2,4-benzenetricarboxylic acid anhydride) as a monomer, are reported to function as film formers in cosmetics, and are reported to be primarily used in nail products. Very limited safety data were available or submitted. The Panel concluded that Adipic Acid/Neopentyl Glycol/Trimellitic Anhydride Copolymer and Phthalic Anhydride/Trimellitic Anhydride/Glycols Copolymer are safe in nail product formulations in the present practices of use and concentration, but the data are insufficient to make a determination of safety on the use of these 2 ingredients in all other types of cosmetic formulations. The Panel also concluded that the available data are insufficient to make a determination that the remaining trimellitic anhydride copolymers are safe for use in cosmetic formulations.
Asunto(s)
Cosméticos , Anhídridos Ftálicos , Animales , Seguridad de Productos para el Consumidor , Cosméticos/efectos adversos , Cosméticos/química , Cosméticos/toxicidad , Humanos , Ratones , Anhídridos Ftálicos/efectos adversos , Anhídridos Ftálicos/química , Anhídridos Ftálicos/toxicidad , Ratas , Pruebas de ToxicidadRESUMEN
Acid anhydrides are used by chemical industries as plasticizers. Trimellitic acid (TMA) is an acid anhydride widely utilized in factories to produce paints, varnishes, and plastics. In addition to causing direct irritant effects, TMA can augment antibody responses in exposed factory workers leading to occupational asthma. Therefore, industries producing TMA have implemented occupational immunosurveillance programs (OISPs) to ensure early diagnosis and medical management, involving exposure reduction/ complete removal of sensitized workers from exposure areas. Multiple animal models (mice strains, rat stains, guinea pig, swine) with different exposure patterns (dermal, nasal, vapor inhalation exposures for different time frames) have been described to elucidate the pathophysiology of TMA exposure. In TMA factories, in spite of implementing advanced environmental controls and personal protective measures to limit exposure, workers become TMA-sensitized. Animal models revealed sIgG, sIgE, sIgA, and sIgM along with pulmonary lesions, cellular infiltrates, alveolar hemorrhage, and pneumonitis associated with TMA exposure. Molecular studies showed involvement of specific functional gene clusters related to cytokine and chemokine responses, lung remodeling, and arginase function. However, thus far, there is no evidence supporting fetotoxic or carcinogenic effects of TMA. OISP data showed IgG and IgE responses in exposed factory workers. Interestingly, timelines for detectable sIgG response, in conjunction with its magnitude, have been shown to be a predictor for future sIgE response. OISPs have been very successful so far at creating a healthy and safe working environment for TMA-exposed factory workers. Graphical Abstract Trimellitic Acid (TMA), used to produce paints, varnishes and plastics, can cause irritant-mediated and immune-mediated occupational health problems. NCBI pubmed search indicated that multiple animal models (different animal types, with chronic vs. acute exposure type, using TMA dust/suspension applied via dermal or other routes) have been used by investigators to elucidate the pathobiology of TMA-exposure. Several outcomes have been measured including humoral, lung/ airway, lymph nodes and dermal/ ear thickening responses. Studies on human subjects have been conducted mostly as parts of Occupational immunosurveillance programs (OISPs) implemented to identify TMA-sensitized workers (using ImmunoCAP and Skin prick testing), monitoring them longitudinally and their medical management including exposure reduction/ complete removal of sensitized workers from exposure areas. Clinical management also includes identification of irritant-induced and/ or immune-mediated outcomes of TMA occupational exposure. Collectively, these studies have led to important insights into the pathomechanism of TMA-exposure and have been very successful at creating a safe working environment for TMA-exposed factory workers.
Asunto(s)
Asma/inmunología , Monitoreo Fisiológico/métodos , Exposición Profesional/efectos adversos , Anhídridos Ftálicos/efectos adversos , Animales , Asma/inducido químicamente , Modelos Animales de Enfermedad , Haptenos , Humanos , Inmunoglobulina E/metabolismo , Salud LaboralRESUMEN
BACKGROUND: Workplace exposure to trimellitic anhydride (TMA) can elicit TMA-specific IgE (sIgE), which may lead to occupational asthma (OA). An occupational immunosurveillance program (OISP) has been implemented to monitor TMA exposure and immunologic outcomes. The purpose of this study was to determine whether TMA-specific IgG (sIgG) responses can discriminate between TMA-exposed workers with and without sIgE responses. METHODS: Serum TMA-specific antibody (IgG, IgG4, and IgE) levels were estimated longitudinally (years 2006 to 2014) in TMA-exposed workers recruited in low, medium, and high exposure areas. sIgG and sIgE titers plotted against exposure duration were compared between workers with (a) sIgG only and (b) with sIgG who developed sIgE. RESULTS: Among 92 TMA-exposed workers continuously monitored for sIgG and sIgE, 38 developed sIgG; 11 developed a sIgE response 342.38 ± 186.03 days posthire and were removed from exposure. The average detection time of sIgG in removed workers (159 ± 92 days) was significantly shorter than for actively exposed workers with only sIgG (346 ± 187 days). Workers with earlier sIgG responses of higher titer (mean value 42.25 µg/mL) compared to delayed responders with lower sIgG titers (mean value 14.79 µg/mL) more frequently developed sIgE responses. Hierarchical clustering showed the initial magnitude and exposure time required for detectable sIgG production discriminated between workers with only sIgG from workers who subsequently produced sIgE. CONCLUSIONS: This study demonstrates the utility of longitudinally monitoring TMA-specific antibodies in an OISP as exposed workers with early sIgG responses and of higher magnitude are more likely to develop TMA sIgE sensitization.
Asunto(s)
Asma Ocupacional/diagnóstico , Inmunoglobulina G/sangre , Monitorización Inmunológica/métodos , Exposición Profesional/análisis , Anhídridos Ftálicos/efectos adversos , Asma Ocupacional/sangre , Asma Ocupacional/inducido químicamente , Humanos , Inmunoglobulina E , Exposición Profesional/efectos adversos , Anhídridos Ftálicos/inmunologíaRESUMEN
A protective effect of allergy for cancer has been suggested, but the results are somewhat conflicting, and the mechanism remains elusive. Interleukin-4 (IL-4) signaling has been identified as a potentially important pathway in the development of allergies and the suppression of cancer development. To evaluate the allergy responses in IL-4-mediated tumor development, we compared the growth of B16F10 melanoma cells in 4% phthalic anhydride (PA)-treated IL-4/Luc/CNS-1 transgenic mice (IL-4 mice) and acetone-olive oil (AOO)-treated IL-4 mice as a control for 3 weeks. Much higher allergic responses and natural killer (NK) and STAT6 activation were found in PA-treated IL-4 mice compared with AOO-treated IL-4 control mice. Tumor volume and weight showed an inverse association with the higher allergic response and were significantly reduced in the PA-treated IL-4 mice when compared with those of AOO-treated IL-4 control mice. Significantly higher activation of STAT6, as well as IL-4 and NK cell activation, was found in the tumor tissues of PA-treated IL-4 mice. Infiltration of immune cells and cytokine levels were also higher in the tumor tissues of PA-treated IL-4 mice. We further found that IL-4-activated NK-92MI cells showed increased anticancer effects in human melanoma cells. Overall, these results showed that allergy responses further accelerated the IL-4-induced inhibition of tumor development through the activation of STAT6 pathways.
Asunto(s)
Interleucina-4/genética , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Activación de Linfocitos/inmunología , Melanoma/etiología , Melanoma/metabolismo , Factor de Transcripción STAT6/metabolismo , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Biomarcadores , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/inmunología , Transformación Celular Neoplásica/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/genética , Hipersensibilidad/inmunología , Inmunohistoquímica , Queratinocitos/inmunología , Queratinocitos/metabolismo , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Melanoma/patología , Melanoma Experimental , Ratones , Ratones Transgénicos , Anhídridos Ftálicos/efectos adversos , ARN Interferente Pequeño/genéticaRESUMEN
AIMS: The purpose of this study was to investigate the effect of Lactobacillus casei variety rhamnosus (LCR35) on Atopic dermatitis (AD)-like symptoms in mice. METHODS AND RESULTS: AD-like skin lesions in BALB/C mice were induced by sensitization and subsequent repeated challenges with trimellitic anhydride (TMA) for 10 days. LCR35 was orally administered to the mice once daily throughout the study. In the TMA-induced AD model, orally administered LCR35 suppressed significantly irritant-related scratching behaviour and skin dehydration as well as apparent severity of AD. LCR35 also significantly decreased serum levels of IgE and IL-4, but not IFN-γ, implying the restoration of TMA-induced disruption of Th1/Th2 balance. Quantitative real-time PCR targeting hypervariable regions of 16S rDNA gene of faecal microbiota indicated that the LCR35 treatment increased the population of Bifidobacterium, Lactobacilli, Enterococcus and Bacteroides fragilis group, but decreased those of Clostridium coccoides group. CONCLUSIONS: LCR35 has the ability to suppress the development of AD in mice, possibly through the modulation of Th1/Th2 balance and gut microbiota. SIGNIFICANCE AND IMPACT OF THE STUDY: LCR35 has a strong potential as a probiotic for preventing AD.
Asunto(s)
Dermatitis Atópica/tratamiento farmacológico , Microbioma Gastrointestinal , Probióticos/administración & dosificación , Administración Oral , Animales , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/microbiología , Dermatitis Atópica/patología , Humanos , Interleucina-4/genética , Interleucina-4/inmunología , Lacticaseibacillus rhamnosus/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Anhídridos Ftálicos/efectos adversos , Reacción en Cadena en Tiempo Real de la Polimerasa , Piel/inmunología , Piel/patologíaRESUMEN
BACKGROUND: Diethylcarbamazine citrate (DEC) is the drug most widely used in the treatment of lymphatic filariasis. Omega-3 fatty acids (ω-3 FAs) are essential polyunsaturated fatty acids and commonly found in marine oils. Both have been applied in treatment of inflammatory diseases but anti-allergic effects should be investigated. OBJECTIVE: The present study was performed to test the effect of both DEC and ω -3 FAs on Trimellitic anhydride (TMA) - induced rat skin allergy. METHODS: In vivo experiment was executed in white albino rats using 100 and 600 mg/ Kg body weight of DEC and ω-3 FAs, respectively in treatment. Ear thickness of sensitized rats to TMA was monitored after challenge. Blood eosinophilia was determined using differential leukocyte count while the appearance of mast cells, eosinophils and collagen fibers in skin tissue were investigated using specific stains. Colorimetric assay of NO was performed in homogenized ears, while expression of inducible nitric oxide synthase (iNOS) was detected using immunohistochemistry. RESULTS: Ear thickness showed a significant (p < 0.05) reduction in both of DEC and ω-3 FAs treated groups. Blood eosinophilia and skin eosinophils were significantly (p < 0.001) decreased by DEC and ?-3 FAs, while the decrease of skin mast cells was only significant (p < 0.01) when ω-3 FAs applied. The expression of iNOS and intensity of stained collagen fibers were decreased obviously by ω-3 FAs but less by DEC treatment. Histopathological observations were more normal in ω-3 FAs than DEC treated groups. CONCLUSION: ω-3 FAs was more potent antiallergic substance against TMA-induced dermatitis than DEC.
Asunto(s)
Alérgenos/efectos adversos , Antialérgicos/farmacología , Dietilcarbamazina/farmacología , Ácidos Grasos Omega-3/farmacología , Hipersensibilidad/tratamiento farmacológico , Anhídridos Ftálicos/efectos adversos , Piel/efectos de los fármacos , Administración Cutánea , Animales , Colágeno/antagonistas & inhibidores , Colágeno/biosíntesis , Oído , Eosinófilos/efectos de los fármacos , Eosinófilos/inmunología , Eosinófilos/patología , Expresión Génica , Humanos , Hipersensibilidad/etiología , Hipersensibilidad/inmunología , Hipersensibilidad/patología , Masculino , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Mastocitos/patología , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Piel/inmunología , Piel/patologíaRESUMEN
BACKGROUND: Contact toxicant reactions are accompanied by localized skin inflammation and concomitant increases in site-specific itch responses. The role(s) of eosinophils in these reactions is poorly understood. However, previous studies have suggested that localized eosinophil-nerve interactions at sites of inflammation significantly alter tissue innervation. OBJECTIVE: To define a potential mechanistic link between eosinophils and neurosensory responses in the skin leading to itching. METHODS: BALB/cJ mice were exposed to different contact toxicants, identifying trimellitic anhydride (TMA) for further study on the basis of inducing a robust eosinophilia accompanied by degranulation. Subsequent studies using TMA were performed with wild type versus eosinophil-deficient PHIL mice, assessing edematous responses and remodeling events such as sensory nerve innervation of the skin and induced pathophysiological responses (ie, itching). RESULTS: Exposure to TMA, but not dinitrofluorobenzene, resulted in a robust eosinophil skin infiltrate accompanied by significant levels of degranulation. Follow-up studies using TMA with wild type versus eosinophil-deficient PHIL mice showed that the induced edematous responses and histopathology were, in part, causatively linked with the presence of eosinophils. Significantly, these data also demonstrated that eosinophil-mediated events correlated with a significant increase in substance P content of the cutaneous nerves and an accompanying increase in itching, both of which were abolished in the absence of eosinophils. CONCLUSIONS: Eosinophil-mediated events following TMA contact toxicant reactions increase skin sensory nerve substance P and, in turn, increase itching responses. Thus, eosinophil-nerve interactions provide a potential mechanistic link between eosinophil-mediated events and neurosensory responses following exposure to some contact toxicants.
Asunto(s)
Eosinófilos/inmunología , Prurito/etiología , Piel/inmunología , Piel/inervación , Alérgenos/administración & dosificación , Alérgenos/inmunología , Animales , Degranulación de la Célula , Colágeno/metabolismo , Dinitrofluorobenceno/administración & dosificación , Dinitrofluorobenceno/efectos adversos , Modelos Animales de Enfermedad , Eosinofilia/inmunología , Eosinofilia/metabolismo , Eosinofilia/patología , Eosinófilos/metabolismo , Fibrosis , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/patología , Ratones , Anhídridos Ftálicos/administración & dosificación , Anhídridos Ftálicos/efectos adversos , Anhídridos Ftálicos/inmunología , Prurito/diagnóstico , Piel/efectos de los fármacos , Piel/patología , Sustancia P/genética , Sustancia P/metabolismoRESUMEN
The interaction between exposure to nanomaterials and existing inflammatory conditions has not been fully established. Multiwalled carbon nanotubes (MWCNT; Nanocyl NC 7000 CAS no. 7782-42-5; count median diameter in atmosphere 61 ± 5 nm) were tested by inhalation in high Immunoglobulin E (IgE)-responding Brown Norway (BN) rats with trimellitic anhydride (TMA)-induced respiratory allergy. The rats were exposed 2 days/week over a 3.5-week period to a low (11 mg/m(3)) or a high (22 mg/m(3)) concentration of MWCNT. Nonallergic animals exposed to MWCNT and unexposed allergic and nonallergic rats served as controls. At the end of the exposure period, the allergic animals were rechallenged with TMA. Histopathological examination of the respiratory tract showed agglomerated/aggregated MWCNT in the lungs and in the lung-draining lymph nodes. Frustrated phagocytosis was observed as incomplete uptake of MWCNT by the alveolar macrophages and clustering of cells around MWCNT. Large MWCNT agglomerates/aggregates were found in granulomas in the allergic rats, suggesting decreased macrophage clearance in allergic rats. In allergic rats, MWCNT exposure decreased serum IgE levels and the number of lymphocytes in bronchoalveolar lavage. In conclusion, MWCNT did not aggravate the acute allergic reaction but modulated the allergy-associated immune response.
Asunto(s)
Nanotubos de Carbono/química , Anhídridos Ftálicos/efectos adversos , Anhídridos Ftálicos/inmunología , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/patología , Administración por Inhalación , Alérgenos/administración & dosificación , Alérgenos/efectos adversos , Animales , Femenino , Inmunoglobulina E/sangre , Pulmón/citología , Pulmón/inmunología , Ganglios Linfáticos/citología , Ganglios Linfáticos/inmunología , Linfocitos/citología , Linfocitos/inmunología , Macrófagos Alveolares/citología , Macrófagos Alveolares/inmunología , Fagocitosis , Anhídridos Ftálicos/administración & dosificación , Ratas , Ratas Endogámicas BN , Hipersensibilidad Respiratoria/inducido químicamenteRESUMEN
Immunosuppressive environmental chemicals may increase the potency of allergens and thereby play a role in the development of allergic diseases. This study's primary objective was to examine the mechanisms behind the relationship between allergic diseases and the immunosuppression induced by some environmental chemicals. We focused on the modulation of allergic potential in vitro and in mice by the organophosphorus pesticide O,O-diethyl-O-4-nitrophenyl-thiophosphate (parathion) and the organochlorine pesticide 1,1,1-trichloro-2,2-bis(4-methoxy-phenyl)ethane (methoxychlor), with respect to the T(H)1-type allergen 2,4-dinitrochlorobenzene (DNCB) and the T(H)2-type allergen trimellitic anhydride (TMA). Mice (4-week-old) were orally administered parathion or methoxychlor. Four weeks after the final dosing, the mice were sensitized to DNCB or TMA, and T-lymphocyte proliferation measured in their (using a local lymph node assay [LLNA]). In addition, we analyzed T-lymphocytes via surface antigen expression and local cytokine production in auricular lymph nodes after treatment with 0.1% DNCB or 0.3% TMA. The estimated concentration of DNCB and TMA to yield a stimulation index (SI) of cell proliferation of three decreased markedly in parathion- and methoxychlor-pre-treated mice. Pesticide pre-treatment induced marked increases in the number of helper and cytotoxic T-cells, levels of T(H)1 and T(H)2 cytokines, and gene expression in lymph node cells. According to our results, T(H)1- and T(H)2-type allergies are aggravated by prior exposure to immunosuppressive environmental chemicals.
Asunto(s)
Dinitroclorobenceno/efectos adversos , Hipersensibilidad a las Drogas/inmunología , Insecticidas/efectos adversos , Irritantes/efectos adversos , Metoxicloro/efectos adversos , Paratión/efectos adversos , Anhídridos Ftálicos/efectos adversos , Células TH1/inmunología , Células Th2/inmunología , Animales , Proliferación Celular/efectos de los fármacos , Dinitroclorobenceno/farmacología , Hipersensibilidad a las Drogas/patología , Femenino , Humanos , Insecticidas/farmacología , Irritantes/farmacología , Células Jurkat , Metoxicloro/farmacología , Ratones , Ratones Endogámicos BALB C , Paratión/farmacología , Anhídridos Ftálicos/farmacología , Células TH1/patología , Células Th2/patologíaRESUMEN
Allergies are immune system disorders characterized by abnormal, acquired sensitivity to various environmental chemicals. We investigated the mechanism of chemical-induced selective type II (T(H)2) allergy by using three different sensitization protocols and the well-known respiratory sensitizer trimellitic anhydride (TMA). Mice were sensitized for either 1, 2, or 3 weeks. For each sensitization schedule, the mice were allocated into 3 or 4 groups: -/- group, both sensitized and challenged with vehicle; -/+ group, sensitized with vehicle and challenged with 0.1% TMA; +/- group, sensitized with 1% TMA and challenged with vehicle; and +/+ group, both sensitized and challenged with 0.1% TMA. After challenge, we assayed the auricular lymph nodes of all mice for number of lymphocytes, surface antigen expression of B-cells, and local cytokine production, and we measured TMA-specific serum IgE levels. Some parameters in mice sensitized for 1 or 2 wk showed, at most, mild changes. In contrast, all parameters in animals receiving 3-wk sensitization showed marked increases, as well as marked increases in the IgE/major histocompatibility complex (MHC) Class II-positive B-cell population and T(H)2 cell production of IL-10 and IL-13. These results indicate that 3 wk of sensitization according to our protocol led to overt respiratory allergic reactions. While these studies showed that using the approach here, positive reactions were elicited using a typical allergen; whether the same events occur after sensitization by other chemicals that are found in the environment remains uncertain. These findings here should be regarded moreover as preliminary in scope and that additional studies with irritants, dermal sensitizers and other respiratory sensitizers are needed to further evaluate the overall sensitivity and selectivity of this novel protocol.
Asunto(s)
Linfocitos B/metabolismo , Hipersensibilidad Respiratoria/inmunología , Células Th2/metabolismo , Animales , Antígenos de Diferenciación/inmunología , Antígenos de Diferenciación/metabolismo , Linfocitos B/inmunología , Linfocitos B/patología , Epítopos , Femenino , Esquemas de Inmunización , Inmunoglobulina E/sangre , Interleucina-10/metabolismo , Interleucina-13/metabolismo , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Anhídridos Ftálicos/administración & dosificación , Anhídridos Ftálicos/efectos adversos , Hipersensibilidad Respiratoria/sangre , Hipersensibilidad Respiratoria/inducido químicamente , Hipersensibilidad Respiratoria/patología , Células Th2/inmunología , Células Th2/patologíaAsunto(s)
Alérgenos/efectos adversos , Cosméticos/efectos adversos , Dermatitis Alérgica por Contacto/diagnóstico , Dermatosis de la Mano/diagnóstico , Dermatitis Alérgica por Contacto/etiología , Dermatitis Alérgica por Contacto/patología , Diagnóstico Diferencial , Párpados/patología , Femenino , Glicoles/efectos adversos , Dermatosis de la Mano/inducido químicamente , Dermatosis de la Mano/patología , Humanos , Labio/patología , Persona de Mediana Edad , Uñas/patología , Cuello/patología , Pruebas del Parche , Anhídridos Ftálicos/efectos adversosRESUMEN
Copolymers or heteropolymers are large molecules with high molecular weights (>1000 D). They have been underestimated for a long time as to their sensitizing capacities. Allergic contact dermatitis to 6 copolymers in cosmetics and 1 in a medical dressing has been described; however, the nature of the hapten is still unknown. We report a case of allergic contact dermatitis to polyvinylpyrrolidone (PVP)/hexadecene copolymer in a purple-colored lipstick and review the literature on allergic contact dermatitis to 7 copolymers: PVP/hexadecene, PVP/eicosene, PVP/1-triacontene, methoxy polyethyleneglycol (PEG)-22/dodecyl glycols, methoxy PEG-17/dodecyl glycols, phthalic anhydride/trimellitic anhydride/glycols, and polyvinyl methyl/maleic acid anhydride.
Asunto(s)
Alérgenos/efectos adversos , Cosméticos/efectos adversos , Cosméticos/química , Dermatitis Alérgica por Contacto/etiología , Polímeros/efectos adversos , Adulto , Humanos , Masculino , Anhídridos Maleicos/efectos adversos , Anhídridos Maleicos/análisis , Excipientes Farmacéuticos/efectos adversos , Excipientes Farmacéuticos/análisis , Anhídridos Ftálicos/efectos adversos , Anhídridos Ftálicos/análisis , Polietilenglicoles/efectos adversos , Polietilenglicoles/análisis , Polímeros/análisis , Polivinilos/efectos adversos , Polivinilos/análisis , Povidona/efectos adversos , Povidona/análogos & derivados , Povidona/análisis , Povidona/química , Tensoactivos/efectos adversos , Tensoactivos/análisisRESUMEN
BACKGROUND: Organic acid anhydrides (OAA) are used as hardeners in epoxy resin systems. They are powerful sensitizers giving frequent rhinitis and asthma in exposed workers. Incidence of symptoms is unknown. Here we present the first prospective study on the associations between OAA exposure, symptoms, and effects of confounding factors. METHODS: All new employees in three plants handling OAA were followed for up to 8.5 years. Before the employment, a questionnaire reporting about symptoms of eyes and airways, smoking habits, and atopy was answered. The subjects were asked at regular medical examinations about work tasks and work-related symptoms. Serum was analysed for specific OAA antibodies. RESULTS: Mean exposures varied between 6 and 39 microg/m3. The incidence for work-related symptoms of the eyes, nose, pharynx, and lower airways was 91, 64, 46, and 31 per 1000 years of exposure, respectively. Symptoms were found frequently, even at mean exposure level at <10 microg/m3. Smoking and atopy increased the risk of symptoms. Immunoglobulin (Ig)E sensitized workers had a significant increased risk for symptoms of the eyes and pharynx and for running nose/sneezing. CONCLUSIONS: Organic acid anhydrides exposure is associated with frequent ocular and airway symptoms even at mean exposure levels at <10 microg/m3. There is an important need for establishment of an occupational threshold limit. A limit value of below 5 microg/m3 is proposed.
Asunto(s)
Oftalmopatías/inducido químicamente , Exposición Profesional , Anhídridos Ftálicos/efectos adversos , Enfermedades Respiratorias/inducido químicamente , Adulto , Oftalmopatías/inmunología , Femenino , Humanos , Hipersensibilidad Inmediata , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Industrias , Masculino , Anhídridos Ftálicos/inmunología , Enfermedades Respiratorias/inmunologíaRESUMEN
BACKGROUND: Occupational asthma can be caused by chemicals. Previously, we established a murine model of immunologically mediated chemical-induced asthma using toluene diisocyanate. OBJECTIVE: We sought to verify this model using trimellitic anhydride (TMA), a respiratory sensitizer, and 1-chloro-2,4-dinitrobenzene (DNCB), a dermal sensitizer. METHODS: BALB/c mice received dermal applications (vehicle or chemical) on days 1 and 7. On day 10, they received an intranasal instillation (vehicle or chemical). Whole-body plethysmography (enhanced pause) was used to monitor changes in ventilatory function and methacholine reactivity. Pulmonary inflammation was assessed by using bronchoalveolar lavage (cells, TNF-alpha levels, and macrophage inflammatory protein 2 levels). Immunologic parameters included total serum IgE levels, lymphocyte distribution in auricular and cervical lymph nodes, and IL-4 and IFN-gamma levels in supernatants of lymph node cells incubated with or without concanavalin A. RESULTS: Mice dermally treated and intranasally challenged with TMA experienced markedly increased enhanced pause immediately after intranasal challenge and increased methacholine reactivity (24 hours later). Mice similarly treated with DNCB did not show any ventilatory changes. Neutrophil influx and increased macrophage inflammatory protein 2 and TNF-alpha levels were found in bronchoalveolar lavage fluid in both TMA- and DNCB-treated mice. The proportion of CD19+ B cells was increased in auricular and cervical lymph nodes of TMA-treated mice. IL-4 and IFN-gamma levels were increased in supernatants of concanavalin A-stimulated auricular and cervical lymph node cells of TMA- or DNCB-treated mice; however, the relative proportions of IL-4 and IFN-gamma levels differed between TMA- and DNCB-treated mice. Serum total IgE levels were increased in TMA-treated mice only. CONCLUSION: Both compounds induce a mixed T(H)1-T(H)2 response, but only TMA induced ventilatory changes. CLINICAL IMPLICATIONS: In the workplace avoiding skin contact with chemical sensitizers might be advised to prevent chemical-induced asthma.
Asunto(s)
Alérgenos/efectos adversos , Asma/inducido químicamente , Dinitroclorobenceno/efectos adversos , Modelos Animales de Enfermedad , Irritantes/farmacología , Anhídridos Ftálicos/efectos adversos , Animales , Asma/patología , Asma/fisiopatología , Citocinas/biosíntesis , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Inmunoglobulina G/clasificación , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Pruebas de Función Respiratoria , Células TH1/efectos de los fármacos , Células TH1/metabolismo , Células Th2/efectos de los fármacos , Células Th2/metabolismoAsunto(s)
Alérgenos/efectos adversos , Cosméticos/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Anhídridos Ftálicos/efectos adversos , Adulto , Dermatitis Alérgica por Contacto/diagnóstico , Dermatosis Facial/inducido químicamente , Femenino , Dermatosis de la Mano/inducido químicamente , Humanos , Persona de Mediana Edad , Enfermedades de la Uña/inducido químicamente , Pintura/efectos adversosRESUMEN
Identification of the chemicals responsible for respiratory and contact allergies in the industrial area is an important occupational safety issue. This study was conducted in mice to determine whether flow cytometry is an appropriate method to analyze and differentiate the specific immune responses to the respiratory sensitizer trimellitic anhydride (TMA) and to the contact sensitizer dinitrochlorobenzene (DNCB) used at concentrations with comparable immunogenic potential. Mice were exposed twice on the flanks (days 0, 5) to 10% TMA or 1% DNCB and challenged three times on the ears (days 10, 11, 12) with 2.5% TMA or 0.25% DNCB. Flow cytometry analyses were conducted on draining lymph node cells harvested on days 13 and 18. Comparing TMA and DNCB immune responses on day 13, we found obvious differences that persisted for most of them on day 18. An increased proportion of IgE+ cells correlated to total serum IgE level and an enhancement of MHC II molecule expression were observed in the lymph node B lymphocytes from TMA-treated mice. The percentage of IL-4-producing CD4+ lymphocytes and the IL-4 receptor expression were clearly higher following TMA exposure. In contrast, higher proportions of IL-2-producing cells were detected in CD4+ and CD8+ cells from DNCB-treated mice. Both chemicals induced a significant increase in the percentage of IFN-gamma-producing cells among CD8+ lymphocytes but to a greater proportion following TMA treatment. In conclusion, this study encourages the use of flow cytometry to discriminate between contact and respiratory sensitizers by identifying divergent expression of immune response parameters.
Asunto(s)
Alérgenos/química , Alérgenos/inmunología , Dinitroclorobenceno/inmunología , Citometría de Flujo/métodos , Anhídridos Ftálicos/inmunología , Administración por Inhalación , Administración Tópica , Alérgenos/efectos adversos , Animales , Citocinas/análisis , Citocinas/metabolismo , Dinitroclorobenceno/efectos adversos , Dinitroclorobenceno/química , Femenino , Antígenos de Histocompatibilidad Clase II/efectos de los fármacos , Antígenos de Histocompatibilidad Clase II/genética , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Ensayo del Nódulo Linfático Local , Ganglios Linfáticos/citología , Ganglios Linfáticos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Anhídridos Ftálicos/efectos adversos , Anhídridos Ftálicos/química , Receptores de Interleucina-4/efectos de los fármacos , Receptores de Interleucina-4/genética , Factores de TiempoRESUMEN
BACKGROUND: Organic acid anhydrides are low molecular weight industrial chemicals, able to cause rhinoconjunctivitis and asthma associated with specific IgE against hapten-carrier protein conjugate. Only a proportion of exposed workers develop IgE-associated allergy to acid anhydrides. OBJECTIVE: We determined whether genetic susceptibility, in particular, HLA Class II alleles may be a risk factor. METHODS: We undertook HLA typing in 52 cases who had confirmed specific IgE and in 73 referents matched on site, age and duration of acid anhydride exposure identified in cross-sectional studies of workers exposed to hexahydrophthalic (HHPA), methylhexahydrophthalic (MHHPA) and methyltetrahydrophthalic (MTHPA) anhydrides. RESULTS: The linked alleles DQ5 (odds ratio [OR]=4.3; 95% confidence interval [95% CI]=1.7, 11) and DR1 (OR 3.0; 95% CI 1.2, 11) were more prevalent in cases than in referents. Within DQ5, DQB1(*)0501 was particularly frequent (OR 3.0; 95% CI 1.2, 7.4). CONCLUSION: DQB1(*)05 gene confers susceptibility to develop specific IgE antibodies against HHPA, MHHPA and a non-significant trend with MTHPA. DQB1(*)0501 is protective for other low molecular chemical sensitizers (isocyanates and plicatic acid) which may indicate varying affinities for the corresponding specific class II molecules.
Asunto(s)
Industria Química , Antígenos HLA-DQ , Antígeno HLA-DR1 , Hipersensibilidad/genética , Enfermedades Profesionales/genética , Anhídridos Ftálicos/efectos adversos , Adulto , Anciano , Alelos , Estudios de Casos y Controles , Intervalos de Confianza , Femenino , Frecuencia de los Genes , Cadenas beta de HLA-DQ , Humanos , Hipersensibilidad/inmunología , Inmunoglobulina E/sangre , Inmunofenotipificación , Masculino , Persona de Mediana Edad , Enfermedades Profesionales/inmunología , Exposición Profesional , Oportunidad Relativa , Compuestos Orgánicos/efectos adversos , Ácidos Ftálicos/efectos adversos , Anhídridos Ftálicos/inmunología , Reacción en Cadena de la Polimerasa/métodos , Medición de RiesgoRESUMEN
BACKGROUND: Trimellitic anhydride (TMA) can induce specific IgE and occupational asthma. The significance of dermal exposure to TMA in immunologic sensitization and on subsequent airway responses is not clearly known. An animal model displaying both an early-phase airway response (EAR) and a late-phase airway response (LAR) after sensitization and subsequent inhalation challenge to a low-molecular-weight chemical has not been previously reported. OBJECTIVE: The present study investigated EAR and LAR after TMA inhalation challenge in Brown Norway rats sensitized by skin exposure to TMA dry powder. METHODS: Twenty milligrams of dry TMA powder was applied to the skin of each clipped rat's dorsum on days 0, 7, 14, and 21 and occluded overnight with surgical tape. Rats were challenged for 10 minutes with 0.2 to 40 mg/m(3) of TMA aerosol after day 35. Enhanced pause (an index of airway resistance) was recorded overnight in a whole-body plethysmography system. Specific IgE and pulmonary eosinophilia were also measured. RESULTS: Concentration-dependent responses to TMA were observed: provocation with 0.2 mg/m(3) produced no response; 1 mg/m(3) induced only EAR; and 5 mg/m(3) and 40 mg/m(3) induced both EAR and LAR. Specific IgE was positive; airway eosinophilic inflammation was observed. CONCLUSION: TMA powder applied to the skin can lead to both immunologic sensitization and subsequent dose-dependent biphasic airway responses after TMA aerosol challenge.