dinitrobenzenes and Dermatitis--Allergic-Contact

Azobenzene disperse dyes (azo DDs) are well-known as textile allergens, but the knowledge of their occurrence in garments is low. The numerous azo DDs and dye components found in textiles constitute a potential health risk, but only seven azo DDs are included in the European baseline patch test series (EBS).. To investigate non-regulated azo DDs and dye components in synthetic garments on the Swedish market.. High-performance liquid chromatography/mass spectrometry, gas chromatography/mass spectrometry and computerized data mining.. Sixty-two azo DDs were detected, with Disperse Red 167:1 occurring in 67%, and 14 other DDs each found in >20% of the garments. Notably, the EBS dyes were less common, three even not detected, while arylamines were frequently detected and exceeded 1 mg/g in several garments. Also, halogenated dinitrobenzenes were identified in 25% of the textiles.. Azo DDs and dye components, in complex compositions and with large variations, occurred frequently in the synthetic garments. The arylamines were shown to occur at much higher levels compared to the azo DDs, suggesting the former constitute a potentially higher health risk. The role of arylamines and halogenated dinitrobenzenes in textile allergy has to be further investigated.

Topics: Allergens; Amines; Azo Compounds; Clothing; Coloring Agents; Dermatitis, Allergic Contact; Dinitrobenzenes; Humans; Patch Tests; Sweden; Textiles

Topics: Animals; Dermatitis, Allergic Contact; Dinitrobenzenes; Dinitrofluorobenzene; Disease Models, Animal; Interleukins; Mice; Mice, Inbred BALB C

Immunoglobulin E (IgE) is involved in the onset of allergic reaction, and the suppression of IgE production leads to alleviation of allergic symptoms. We found that mango peel ethanol extract (MPE) significantly suppresses IgE production by human myeloma cell line U266 cells, suggesting that MPE has an anti-allergic effect by inhibiting the production of IgE. Although mangiferin is contained in mango, which suppresses IgE production by U266 cells, it was not contained in MPE. We investigated the suppressive effect of MPE in 2,4-dinitrofluorobenzene (DNFB)-induced allergic contact dermatitis model mice. The elevation of serum IgE level was significantly suppressed by oral administration of MPE. Intake of MPE also suppressed the expression level of IL-4 in the DNFB-challenged ears, suggesting that MPE suppresses the IL-4-mediated maturation into IgE-producing cells. Our findings indicate that MPE has a potential to alleviate the increase in serum IgE level that is feature of type I allergy.

Topics: Animals; Cell Line, Tumor; Dermatitis, Allergic Contact; Dinitrobenzenes; Disease Models, Animal; Ear; Ethanol; Gene Expression; Humans; Immunoglobulin Class Switching; Immunoglobulin E; Interleukin-4; Mangifera; Mice, Inbred BALB C; Plant Extracts

Allergic contact dermatitis is the most frequent occupational disease in industrialized countries. It is caused by CD8(+) T cell-mediated contact hypersensitivity (CHS) reactions triggered at the site of contact by a variety of chemicals, also known as weak haptens, present in fragrances, dyes, metals, preservatives, and drugs. Despite the myriad of potentially allergenic substances that can penetrate the skin, sensitization is relatively rare and immune tolerance to the substance is often induced by as yet poorly understood mechanisms. Here we show, using the innocuous chemical 2,4-dinitrothiocyanobenzene (DNTB), that cutaneous immune tolerance in mice critically depends on epidermal Langerhans cells (LCs), which capture DNTB and migrate to lymph nodes for direct presentation to CD8(+) T cells. Depletion and adoptive transfer experiments revealed that LCs conferred protection from development of CHS by a mechanism involving both anergy and deletion of allergen-specific CD8(+) T cells and activation of a population of T cells identified as ICOS(+)CD4(+)Foxp3(+) Tregs. Our findings highlight the critical role of LCs in tolerance induction in mice to the prototype innocuous hapten DNTB and suggest that strategies targeting LCs might be valuable for prevention of cutaneous allergy.

Topics: Allergens; Animals; Antigen Presentation; Antigens, CD; CD8-Positive T-Lymphocytes; Cell Communication; Cell Movement; Cells, Cultured; Dermatitis, Allergic Contact; Dinitrobenzenes; Epidermis; Forkhead Transcription Factors; Immune Tolerance; Inducible T-Cell Co-Stimulator Protein; Langerhans Cells; Lymph Nodes; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Transgenic; T-Lymphocytes, Regulatory

Dendritic cell (DC) maturation in response to contact sensitizers is a crucial step in the induction of sensitization reactions; however the underlying mechanism of activation remains unknown. To test whether the extent of protein haptenation is a determinant in DC maturation, we tested the effect of five dinitrophenyl (DNP) analogues of different reactivity, on maturation markers in the cell line, THP-1. The potencies of the test compounds in upregulating CD54 levels, inducing IL-8 release and triggering p38 MAPK phosphorylation did not correlate with their ability to deplete intracellular glutathione (GSH) levels or cause cell toxicity. However, the compounds' potency at inducing p38 phosphorylation was significantly associated with the amount of intracellular protein adducts formed (p<0.05). Inhibition experiments show that, at least for DNFB, p38 MAP kinase signalling controls compound-specific changes in CD54 expression and IL-8 release. 2D-PAGE analysis revealed that all the DNP analogues appeared to bind similar proteins. The analogues failed to activate NFkB, however, they activated Nrf2, which was used as a marker of oxidative stress. Neither GSH depletion, by use of buthionine sulfoximine, nor treatment with the strongly lysine-reactive hapten penicillin elicited maturation. We conclude that protein haptenation, probably through reactive cysteine residues may be a trigger for maturation events in this in vitro model and that p38 activation may be a discriminatory marker for the classification of potency of chemical sensitizers.

Topics: Antigen Presentation; Cell Line, Tumor; Dendritic Cells; Dermatitis, Allergic Contact; Dinitrobenzenes; Glutathione; Haptens; Humans; Leukemia, Monocytic, Acute; p38 Mitogen-Activated Protein Kinases; Signal Transduction; Xenobiotics

Patch testing is the confirmatory procedure for allergic contact dermatitis. The test requires the application of chemicals under occlusion for approximately 48 hours to maximize penetration, although it can also produce irritation. Photomechanical waves (PW) have been shown to render the stratum corneum transiently permeable and facilitate the delivery of macromolecules into the epidermis. This alternative might reduce prolonged occlusion of the skin to minimize irritancy, while retaining the sensitivity of the test.. PW was used to facilitate the delivery of an allergen into the skin in vivo.. The allergic skin reaction using PW delivery was compared with 5-minute and 21-hour occlusion in a sensitized hairless albino guinea pig model. The pigs were sensitized by intradermal injection of (0.01%) dinitrochlorobenzene (DNCB) and topical administration (0.1%, 1 week later) of the hapten. One month later, testing for the allergic response was performed by the administration with PW of 10 microL of 0.1% DNCB.. Our results show that there was an allergic reaction for the 24 hour occlusion or PW delivery of the antigen. In contrast, no response was observed for the 5-minute occlusion with the antigen.. The rapid delivery of antigens with PW can improve the test for the diagnosis of contact dermatitis.

Topics: Allergens; Animals; Dermatitis, Allergic Contact; Dinitrobenzenes; Disease Models, Animal; Drug Delivery Systems; Female; Guinea Pigs; Patch Tests

The study was performed to investigate effects of the phosphodiesterase 4 inhibitor RPR 73401 [N-(3, 5-dichloropyrid-4-yl)-3-cyclopentyl-oxy-4-methoxybenzamid] on an allergic skin reaction. To simulate an immunological inflammation, BALB/c mice were sensitized to dinitrochlorobenzene or toluenediisocyanate. At first, the abdominal skin was shaved and 50 microliter Freund's adjuvant were injected intracutaneously once. Then, the horny layer was removed by adhesive tape stripping and 100 microliter 0.5% dinitrochlorobenzene or 5% toluenediisocyanate were administered on the epidermis for 4 days. After repeated local treatment of the ear skin with 20 microliter 3% RPR 73401 or intraperitoneal administration of 1 and 5 mg/kg RPR 73401, 20 microliter 1% dinitrochlorobenzene or 0.5% toluenediisocyanate were given topically as a challenge. The vehicle controls showed a high increase in ear thickness over 48 h after challenge, whereas RPR 73401 administered on either route reduced this increase significantly. Nevertheless after topical administration, RPR 73401 had a longer lasting effect. These and other results may point to an indication for RPR 73401 in immunological dermatitis.

Topics: Administration, Topical; Animals; Benzamides; Cyclosporine; Dermatitis, Allergic Contact; Dinitrobenzenes; Disease Models, Animal; Female; Interleukin-4; Mice; Mice, Inbred BALB C; Phosphodiesterase Inhibitors; Pyridines; Toluene 2,4-Diisocyanate

The dinitrohalobenzenes are known to cause skin sensitization and have been used in many seminal investigations of the relationships between physicochemical characteristics and sensitizing potential. The electrophilic theory of skin sensitization implies that contact allergic potential should correlate positively with ability of chemicals to react with proteins to form immunogenic hapten-protein conjugates. It is intriguing, therefore, that previous studies in guinea pigs and mice have suggested that such correlations do not apply to dinitrohalobenzenes. To address this, we have examined, using the murine local lymph node assay (LLNA), the sensitizing activity of 2,4-dinitrofluorobenzene (DNFB), 2,4-dinitrochlorobenzene (DNCB), 2,4-dinitrobromo-benzene (DNBB) and 2,4-dinitroiodobenzene (DNIB). In contrast to previous investigations, it was found that the ability of these chemicals to provoke responses in the LLNA correlated closely with their reported protein reactivity. On the basis of these data, it is proposed that dinitrohalobenzenes conform to the electrophilic theory of skin sensitization and that they should be regarded as direct acting haptens.

Topics: Allergens; Animals; Dermatitis, Allergic Contact; Dinitrobenzenes; Dose-Response Relationship, Drug; Lymph Nodes; Mice; Mice, Inbred BALB C; Skin Tests

When one or two drops of a dilute, non-irritating solution of 2,4-dinitrochlorobenzene (DNCB) is applied to a small area of skin of the intact guinea pig, about 20 per cent of the applied material, or some derivative of it, is soon excreted in urine. In normal, as well as in specifically sensitized guinea pigs, DNCB at the site of local application becomes rapidly bound to skin protein through primary chemical bonds. Twenty-four hours after application roughly half of the material present at the local skin site is still extractable with organic solvents. Of the non-extractable dinitrophenyl groups, about 99 per cent are in epidermis, and about 85 per cent are substituted in epsilon-NH(2) groups of lysine residues. Only traces of bound dinitrophenyl groups were observed in the corium. It is uncertain whether these are formed in situ, or are experimental contaminants, or are migratory epidermally formed conjugates. Even when DNCB is injected intradermally it combines predominantly with overlying epidermis and with epidermal components of hair follicles, but only slightly with corium. The 2,4-dinitrophenyl conjugates which are localized in the deeper, viable half of the epidermis, close to the epidermal-dermal junction, are inferred to be the agents responsible for specifically evoking the allergic response in sensitized animals. Conjugates which are situated in the outer, cornified half of the epidermis are shown to be incapable of eliciting the allergic response. The results furnish a basis for interpreting a common pattern of lesions in allergic contact dermatitis as it occurs spontaneously in man.

Topics: Animals; Dermatitis; Dermatitis, Allergic Contact; Dermatitis, Contact; Dinitrobenzenes; Dinitrochlorobenzene; Epidermis; Guinea Pigs; Humans; Hypersensitivity; Male; Nitrobenzenes; Proteins; Skin; Skin Physiological Phenomena