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The anti-inflammatory, antiviral, and anti-cancer properties, as well as the mechanism of action of cyclo-[Pro-Pro-ß3-HoPhe-Phe-] tetrapeptide (denoted as 4B8M), were recently described. The aim of this work was to synthesize and evaluate the immunosuppressive actions of the stereochemical variants of 4B8M by sequential substitution of L-amino acids by D-amino acids (a series of peptides denoted as P01-P07) using parent 4B8M as a reference compound. In addition, diverse available bioinformatics tools using machine learning and artificial intelligence were tested to find the bio-pharmacokinetic and polypharmacological attributes of analyzed stereomers. All peptides were non-toxic to human peripheral blood mononuclear cells (PBMCs) and only cyclo-[D-Pro-Pro-ß3-HoPhe-Phe-] peptide (P03) was capable of inhibiting mitogen-induced PBMC proliferation. The peptides inhibited the lipopolysaccharide (LPS)-induced production of tumor necrosis factor-alpha (TNF-α) to various degrees, with P04 (cyclo-[Pro-Pro-D-ß3-HoPhe-Phe-]) and P03 being the most potent. For further in vivo studies, P03 was selected because it had the combined properties of inhibiting cell proliferation and TNF-α production. P03 demonstrated a comparable ability to 4B8M in the inhibition of auricle edema and lymph node cell number and in the normalization of a distorted blood cell composition in contact sensitivity to the oxazolone mouse model. In the mouse model of carrageenan-induced inflammation of the air pouch, P03 exhibited a similar inhibition of the cell number in the air pouches as 4B8M, but its inhibitory effects on the percentage of neutrophils and eosinophils in the air pouches and blood, as well as on mastocyte degranulation in the air pouches, were stronger in comparison to 4B8M. Lastly, in a mouse model of dextran sulfate-induced colitis, similar effects to 4B8M regarding thymocyte number restoration and normalization of the blood cell pictures by P03 were observed. In summary, depending on either experimental findings or in silico predictions, P03 demonstrated comparable, or even better, anti-inflammatory and bio-pharmacokinetic properties to 4B8M and may be considered as a potential therapeutic. The possibility of P00 and P03 identification by circular dichroism measurements was tested by quantum-chemical calculations.
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Yolkin, an egg yolk immunoregulatory protein, stimulates the humoral but inhibits the cellular immune response in adult mice. The aim of this investigation was to evaluate the effects of yolkin administration on the immune response using a model of juvenile, i.e., 28-day- and 37-day-old, mice. We examined the yolkin influence on the magnitude of the cellular immune response, which was determined as contact sensitivity (CS) to oxazolone (OXA), and the humoral immune response, which was determined as the antibody response to ovalbumin (OVA). Yolkin was administered in drinking water, followed by immunization with OXA or OVA. In parallel, the phenotypic changes in the lymphoid organs were determined following yolkin treatment and prior immunization. The results showed that yolkin had a stimulatory effect on CS in the mice treated with yolkin from the 37th day of life but not from the 28th day of life. In contrast, no regulatory effect of yolkin on antibody production was found in 28-day- and 37-day-old mice. Phenotypic studies revealed significant changes in the content of B cells and T cell subpopulations, including CD4+CD25+Foxp3 regulatory T cells. The association between the effects of yolkin on the magnitude of CS and phenotypic changes in main T- and B-cell compartments, as well the importance of changes in T-regulatory and CD8+ cells in the age categories, are discussed. We conclude that the immunoregulatory effects of yolkin on the generation of CS in mice are age dependent and change from stimulation in juvenile to suppression in adult mice.
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Ovalbúmina , Animales , Ratones , Ovalbúmina/inmunología , Fenotipo , Oxazolona , Femenino , Inmunidad Humoral/efectos de los fármacos , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos B/inmunología , Linfocitos B/efectos de los fármacos , Inmunidad Celular/efectos de los fármacos , Factores de Edad , Dermatitis por Contacto/inmunología , Envejecimiento/inmunologíaRESUMEN
Although subtle barrier defects may facilitate allergen penetration, thereby enabling allergic sensitization, the relationship between sweating disturbance and skin barrier function is unknown. However, many studies on contact hypersensitivity in mice examined ear skin, which does not sweat, instead of the footpad, where sweating is uniquely present. In this study, we assessed whether sweat suppression in the footpad before hapten application provoked a skin barrier abnormality and reduced inflammatory thresholds to topical haptens. Mice without any genetic skin barrier dysfunction displayed markedly reduced inflammatory thresholds to haptens under transient sweat suppression before hapten application. Epicutaneously applied haptens penetrated the skin more robustly in the presence of sweat suppression compared with that in its absence, although this increase was abolished by exposure to high-humidity conditions. These mice displayed a subtle atopic dermatitis-like inflammation mediated by type 2 response-dominant inflammation and increased IgE responses, mimicking some events occurring in nonlesional atopic dermatitis skin in humans and in murine models. These lesions were dramatically attenuated by exposure to high-humidity conditions. In our model, hapten sensitization does not require mechanical injury, explaining why sensitization occurs through nonlesional atopic dermatitis skin. Awareness of the importance of preserving sweating responses is essential to prevent occupational contact dermatitis and atopic dermatitis.
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Összefoglaló. Bevezetés: A nikkel szélesköruen elterjedt fém és kontaktallergén. Megtalálható mindennapi használati tárgyainkban, feldolgozza az ipari termelés, és az egészségügyben is rendre bovül alkalmazási köre. Egyidejuleg a társadalom növekvo hányadánál fordul elo nikkel-kontaktszenzibilizáció. Célkituzés: Az epicutan tesztelt betegcsoport adatainak feldolgozása, kiemelve a nikkelpozitív betegek megoszlását nem, életkor, diagnózis, a klinikai tünetek lokalizációja és a társult fémérzékenység szerint, továbbá a 2004 óta érvényes európai uniós Nikkel Direktívák hatásainak tanulmányozása. Módszer: A közlemény a Semmelweis Egyetem Bor-, Nemikórtani és Boronkológiai Klinikájának Allergológia Laboratórium és Szakambulanciáján 1994-tol 2014-ig 13 693 fo (10-87 év közötti) standard környezeti epicutan sorral tesztelt beteg adatait vizsgálja retrospektív módon. Eredmények: Az összes vizsgált borbeteg nikkelszenzibilizációs aránya 1994-ben 13,1%, 2004-ben 11,5%, 2014-ben 19,1% volt. A nikkel-kontaktdermatitis foként nobetegeknél (93,0%) fordul elo. A klinikai tünetek elsosorban a karokra és az arcra lokalizálódnak. Nikkelérzékenyeknél az allergiás kontaktdermatitis diagnózisa 65,8%, atopiás dermatitis 9,7%-nál fordul elo. A nikkelérzékenységhez leggyakrabban társult fémallergének a kobalt és a króm. Az 1994-2004-es periódushoz képest az európai uniós Nikkel Direktívákat követo 10 évben a szenzibilizáció százalékos emelkedése szignifikáns volt, ugyanakkor a nikkelpozitívak évenkénti száma csökkent. 1994-ben a betegek legnagyobb hányada (26,5%) a 20-24 éves korcsoportba tartozott, 2004-ben szintén (20,8%), 2014-ben azonban a 35-39 éves korosztályhoz (15,1%). Következtetések: A nikkelszenzibilizáció korban eltolódást mutat az idosebb korosztály felé, a 35 évesnél fiatalabb betegek száma mérséklodött. A Nikkel Direktívák révén a fiatalabbak késobbi életkorban és kisebb mértéku nikkelexpozíciónak vannak kitéve. A vizsgált betegek nikkelérzékenységének százalékos emelkedése miatt azonban újabb szabályozások bevezetése és a hatályban lévok módosítása szükségszeru. Orv Hetil. 2021; 162(16): 629-637. INTRODUCTION: Nickel is a widely used metal and contact allergen. It can be found in our everyday objects and it is becoming more prevalent in healthcare. Simultaneously, nickel contact sensitization occurs more frequently. OBJECTIVE: Analysis of data of patch tested patients by gender, age, diagnosis, localization of skin lesions, and associated metal sensitivity. Furthermore, to study the effects of the European Nickel Directives in force since 2004. METHOD: Retrospective analysis of data of 13 693 patients (aged 10-87) tested with a standard series of contact allergens at the Allergy Outpatient Unit and Laboratory of the Department, Venereology and Dermatooncology, Semmelweis University. RESULT: Nickel sensitization of all examined patients was 13.1% in 1994, 11.5% in 2004, and 19.1% in 2014. Contact dermatitis occurred mainly in females (93.0%). Skin lesions are primarily localized to the arms and face. Diagnosis of allergic contact dermatitis occurred in 65.8%, and atopic dermatitis in 9.7% of tested patients. Commonly associated metal sensitivities were cobalt and chromium. In the 10 years following the Nickel Directives, the increase of the ratio of sensitized patients was significant while the number of nickel-positives per year decreased. Both in 1994 and 2004, the largest proportion of patients belonged to the 20-24 age group (26.5% and 20.8%, respectively), but in 2014, to the 35-39 age group (15.1%). CONCLUSION: Nickel sensitization shifts towards the older age group, with a decrease in young patients. Because of the Nickel Directives, people are exposed to nickel at a later age and to a lesser extent. Due to the increase of the ratio of nickel-sensitive patients, it is necessary to introduce new regulations and amend the existing ones. Orv Hetil. 2021; 162(16): 629-637.
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Dermatitis Alérgica por Contacto/epidemiología , Níquel/efectos adversos , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Europa (Continente)/epidemiología , Unión Europea , Femenino , Humanos , Persona de Mediana Edad , Pacientes Ambulatorios , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Antibiotics, while eliminating pathogens, also partially deplete commensal bacteria. Antibiotic-induced dysbiosis may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. The aim of this study is to investigate the impact of perinatal antibiotic treatment on T cell-mediated immune response in adult mice. METHODS: Oral treatment with broad-spectrum antibiotic enrofloxacin during gestation and breastfeeding or breastfeeding or gestation alone was used to evaluate whether antibiotic exposure early in life could modulate contact sensitivity (CS) in adult mice. RESULTS: Here, we demonstrated that enrofloxacin treatment during gestation and breastfeeding, but not during pregnancy or breastfeeding alone, aggravated CS reaction in adult mice measured by ear swelling. These data correlate with increased myeloperoxidase (MPO) activity in the ear extracts and elevated production of IL-6 and IL-17A by auricular lymph node cells (ELNC) and was not influenced by food consumption and body weight. In each dosing regimen, enrofloxacin treatment reduced the relative abundance of Enterococcus spp. but did not influence the relative abundances of Lactobacillus, Clostridium cluster XIVa, XIVab, I, Bacteroidetes, and segmented filamentous bacteria (SFB). However, prolonged enrofloxacin-treatment during both gestation and breastfeeding decreased the relative abundance of Clostridium cluster IV. CONCLUSION: These data show that long-term perinatal enrofloxacin treatment induces intestinal dysbiosis, characterized by decreased levels of anti-inflammatory Clostridium cluster IV, and alters T cell-dependent immune responses, enhancing CS reaction in adult mice.
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Antibacterianos/toxicidad , Dermatitis por Contacto/etiología , Disbiosis/etiología , Enrofloxacina/toxicidad , Administración Oral , Animales , Antibacterianos/administración & dosificación , Clostridium/aislamiento & purificación , Dermatitis por Contacto/inmunología , Disbiosis/inmunología , Enrofloxacina/administración & dosificación , Femenino , Lactancia , Masculino , Ratones , Ratones Endogámicos BALB C , Embarazo , Efectos Tardíos de la Exposición Prenatal/etiología , Efectos Tardíos de la Exposición Prenatal/inmunología , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Prevalences of sensitivity to contact allergens change over time as a result of variations in allergen exposure. OBJECTIVES: The aim of the study was to describe trends in sensitisation to allergens of the European baseline series in Turkey between 2013 and 2019. METHODS: The patch test results of 1309 patients with suspected allergic contact dermatitis (ACD) were analysed retrospectively, and the prevalence of contact allergies to European baseline series allergens was compared with previous data (for 1998-2005). RESULTS: A total of 534 (40.8%) patients exhibited one or more positive patch test reaction. The five most frequent allergens were nickel sulfate (19.6%), potassium dichromate (6.5%), cobalt chloride (6%), Myroxylon pereirae resin (5%), and p-phenylenediamine (PPD; 3.7%). Statistically significant increases in the prevalence of sensitisation to methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; P < .001), Myroxylon pereirae resin (P < .001), PPD (P = .008), and fragrance mix I (P = .036) were observed in the 2013 to 2019 period compared with the 1998 to 2005 period. Conversely, positive reactions to neomycin sulfate (P = .029), clioquinol (P = .031), and primin (P = .001) decreased significantly. CONCLUSION: This study provides a comprehensive profile of ACD in Turkey. The remarkable increase in the MI and MCI/MI contact allergy observed underlines the urgent need for regulatory measures to reduce exposure to MI and MCI/MI in Turkey.
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Dermatitis Alérgica por Contacto/diagnóstico , Dermatitis Alérgica por Contacto/epidemiología , Pruebas del Parche , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Alérgenos/efectos adversos , Niño , Preescolar , Dermatitis Alérgica por Contacto/etiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conservadores Farmacéuticos/efectos adversos , Prevalencia , Estudios Retrospectivos , Distribución por Sexo , Turquía/epidemiología , Adulto JovenRESUMEN
Yolkin is a product of proteolytic degradation of vitellogenin, a protein contained in eggs' yolk, with already described procognitive properties. Here, we investigated effects of yolkin on the humoral and cellular immune response in mice, phenotype of cells from lymphoid organs and function of innate immunity cells. In vitro studies included effects of yolkin on mitogen-induced thymocyte proliferation, percentage of CD19 cells in bone marrow cells culture, expression of signaling molecules in Jurkat cells, interleukin 2 receptor (IL-2R) subunits in WEHI 231 cells and susceptibility of these cells to anti-Ig-induced cell death. The results showed that repeatable i.p. injections of yolkin stimulated the humoral immune response to sheep red blood cells (SRBC) irrespective of the time of the treatment. On the other hand, yolkin inhibited contact sensitivity to oxazolone. Treatment of mice with yolkin diminished the percentage of double positive cells and increasing the content of single positive CD4+ and CD8+ cells in the thymus. At the same time an increase of percentage of CD19 + B cells in the spleen and mesenteric lymph nodes was observed. In addition, the protein, given i.p., diminished ex vivo ability to synthesize nitric oxide by resident, peritoneal macrophages, stimulated with lipopolisaccharide (LPS). In vitro studies showed that yolkin increased CD19+ cell content in bone marrow cell population. The protein also enhanced proliferation of thymocytes to concanavalin A and stimulated expression of MAP kinases in Jurkat cells. In WEHI 231 B cell line yolkin caused a loss of IL-2R gamma chain expression, correlated with an increased resistance of these cells to proapoptotic action of anti-Ig antibodies. In conclusion, this is a first demonstration of immunotropic properties of yolkin in in vitro and in vivo tests. The results provide evidence for induction of maturation and stimulatory signals in immature T and B cells by the protein, suggesting its potential role in the development of an embryo's immune system.
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Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Vitelogeninas/inmunología , Vitelogeninas/farmacología , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Femenino , Humanos , Células Jurkat , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/inmunología , Activación de Linfocitos/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Ovinos , Bazo/inmunología , Timocitos/efectos de los fármacos , Timocitos/inmunología , Timo/inmunologíaRESUMEN
Purpose: The aetiology of pigmented purpuric dermatoses is unclear. Recent studies speculate about contact sensitivity to play a role in the aetiology of the disease. In most patients, the lesions begin and stay limited on the lower extremities as textile products are in tight contact with the skin. Also, textile dyes can cause contact dermatitis of purpuric type. This study was conducted in order to understand whether the contact sensitivity plays a critical role in the aetiology of pigmented purpuric dermatoses. Materials and methods: Patients with diagnosis of pigmented purpuric dermatoses were included in the study. Patch tests were applied at the back of all patients with textile series (Chemotechnique Diagnostics TF-1000) which have 33 allergens containing textile dyes, material and protectors by IQ Ultra Chamber. Test sites were evaluated at 48, 72, 96. h and on the 7th day according to the criteria of the International Contact Dermatitis Research Group. The evaluation results were recorded in patient files and the results were statistically compared. Results: Eighteen males (60%) and 12 females (40%), a total of 30 patients were included in the study. Schamberg disease in 23 patients (76.7%), lichen aureus in 5 patients (16.7%) and Majocchi disease in 2 patients (6.7%) were described out of total 30 patients. No contact sensitivity was detected in any of the patients. Conclusion: Contact sensitivity to textile dyes was not found as an etiologic factor in our study group.
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Alérgenos/administración & dosificación , Colorantes/administración & dosificación , Dermatitis Alérgica por Contacto , Trastornos de la Pigmentación/etiología , Púrpura/etiología , Textiles , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas del Parche , Trastornos de la Pigmentación/diagnóstico , Púrpura/diagnóstico , Adulto JovenRESUMEN
BACKGROUND: Cyclophosphamide (CY) is one of the most widely used alkylating agents in the treatment of various cancers and some autoimmune diseases. Numerous reports suggest that CY exerts immunoregulatory effects. Animal studies have shown CY affects contact sensitivity (CS) response by depleting CD4+CD25+ T regulatory cells and CD8+ T suppressor (Ts) cells. In a mouse model of CS, we previously showed that in vivo treatment with CY shapes the immunogenic/immunoregulatory balance of peritoneal macrophages. The aim of the current study is to verify if macrophages (Mf) from CY-treated mice are indeed able to induce immunoregulatory cells that could protect from suppression. METHODS: Adoptive cell transfer of CS was used to examine immunomodulating properties of peritoneal Mf from CY-treated mice. Isolation of peritoneal Mf from animals that were (Mf-CY) or were not (Mf) treated with CY were cultured to identify cytokine repertoire. Further, we assessed spleen cell (SPLC) cytokine production following immunization with trinitrophenyl-conjugated Mf from donors treated (TNP-Mf-CY) or non-treated (TNP-Mf) with CY. RESULTS: In vitro experiments identified that Mf-CY produce more IL-6, TNF-α and TGF-ß than naïve Mf. Further, immunization with peritoneal TNP-Mf-CY induces CD4+ T contrasuppressor cells (Tcs) cells that protect CS-effector cells from suppression. Higher IL-17A secretion was observed from TNP-Mf-CY-treated mouse SPLC compared to SPLC from TNP-Mf injected mice suggesting that this cytokine might be important in mediating contrasuppression in this model. CONCLUSIONS: Our results show that in vivo treatment with CY influences mouse peritoneal Mf to induce CD4+ Tcs cells that protect CS-effector cells from suppressive signals of Ts cells.
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Linfocitos T CD4-Positivos/inmunología , Ciclofosfamida/farmacología , Dermatitis por Contacto/inmunología , Macrófagos Peritoneales/inmunología , Animales , Células Cultivadas , Citocinas/metabolismo , Inmunización , Ratones , Bazo/metabolismo , Subgrupos de Linfocitos T/inmunología , Trinitrobencenos/farmacologíaRESUMEN
BACKGROUND: Genetic background influences allergic immune responses to environmental stimuli. Non-obese diabetic (NOD) mice are highly susceptible to environmental stimuli. Little is known about the interaction of autoimmune genetic factors with innate immunity in allergies, especially skin hypersensitivity. OBJECTIVES: To study the interplay of innate immunity and autoimmune genetic factors in contact hypersensitivity (CHS) by using various innate immunity-deficient NOD mice. METHODS: Toll-like receptor (TLR) 2-deficient, TLR9-deficient and MyD88-deficient NOD mice were used to investigate CHS. The cellular mechanism was determined by flow cytometry in vitro and adoptive cell transfer in vivo. To investigate the role of MyD88 in dendritic cells (DCs) in CHS, we also used CD11cMyD88+ MyD88-/- NOD mice, in which MyD88 is expressed only in CD11c+ cells. RESULTS: We found that innate immunity negatively regulates CHS, as innate immunity-deficient NOD mice developed exacerbated CHS accompanied by increased numbers of skin-migrating CD11c+ DCs expressing higher levels of major histocompatibility complex II and CD80. Moreover, MyD88-/- NOD mice had increased numbers of CD11c+ CD207- CD103+ DCs and activated T effector cells in the skin-draining lymph nodes. Strikingly, re-expression of MyD88 in CD11c+ DCs (CD11cMyD88+ MyD88-/- NOD mice) restored hyper-CHS to a normal level in MyD88-/- NOD mice. CONCLUSION: Our results suggest that the autoimmune-prone NOD genetic background aggravates CHS regulated by innate immunity, through DCs and T effector cells.
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Dermatitis por Contacto/genética , Inmunidad Innata/genética , Traslado Adoptivo , Animales , Antígeno B7-1/metabolismo , Movimiento Celular , Citocinas/inmunología , Citocinas/metabolismo , Células Dendríticas/citología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Dermatitis por Contacto/etiología , Dermatitis por Contacto/inmunología , Antígenos de Histocompatibilidad Clase II/metabolismo , Inmunidad Innata/inmunología , Ganglios Linfáticos/citología , Ganglios Linfáticos/inmunología , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Ratones Noqueados , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/inmunología , Cloruro de Picrilo/efectos adversos , ARN Mensajero/metabolismo , Piel/citología , Piel/inmunología , Piel/metabolismo , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/inmunología , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/inmunología , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/inmunologíaRESUMEN
BACKGROUND: Rosacea is a common dermatosis characterized by erythema, telangiectasia, papules and pustules. OBJECTIVE: We aimed to evaluate contact sensitivity in the rosacea patients. METHODS: We included 65 rosacea patients and 60 healthy volunteers in the study. The patient and control groups were patch tested with European baseline series and cosmetic series. RESULTS: A positive reaction to at least 1 allergen in the European standard series was found in 32.3% of rosacea patients and 20.0% of subjects in the control group while the relevant numbers were 30.8% of rosacea patients and 10% of controls with the cosmetic series (p=0.08). In total, we found a positive reaction to at least 1 allergen in 38.5% of patients and 25.0% of controls (p=0.15). We did not find a statistically significant relationship between a positive reaction to 1 allergen in total and the gender, skin type, rosacea type, ocular involvement, age and disease duration. There were more symptoms in patients with a positive reaction to allergens (p<0.001). CONCLUSION: Contact sensitivity was detected more common in rosacea patients. Patch testing may be useful in the treatment and follow up of rosacea patients especially if symptoms such as itching, burning and stinging are present.
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BACKGROUND: Rosacea is a common dermatosis characterized by erythema, telangiectasia, papules and pustules. OBJECTIVE: We aimed to evaluate contact sensitivity in the rosacea patients. METHODS: We included 65 rosacea patients and 60 healthy volunteers in the study. The patient and control groups were patch tested with European baseline series and cosmetic series. RESULTS: A positive reaction to at least 1 allergen in the European standard series was found in 32.3% of rosacea patients and 20.0% of subjects in the control group while the relevant numbers were 30.8% of rosacea patients and 10% of controls with the cosmetic series (p=0.08). In total, we found a positive reaction to at least 1 allergen in 38.5% of patients and 25.0% of controls (p=0.15). We did not find a statistically significant relationship between a positive reaction to 1 allergen in total and the gender, skin type, rosacea type, ocular involvement, age and disease duration. There were more symptoms in patients with a positive reaction to allergens (p < 0.001). CONCLUSION: Contact sensitivity was detected more common in rosacea patients. Patch testing may be useful in the treatment and follow up of rosacea patients especially if symptoms such as itching, burning and stinging are present.
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Humanos , Alérgenos , Mordeduras y Picaduras , Quemaduras , Dermatitis por Contacto , Eritema , Estudios de Seguimiento , Voluntarios Sanos , Pruebas del Parche , Prurito , Rosácea , Piel , Enfermedades de la Piel , TelangiectasiaRESUMEN
Contact hypersensitivity (CHS) in rodents and contact dermatitis in humans are long-known pathological conditions caused by MHC-restricted T-cell responses. These responses are triggered upon T-cell recognition of neo-antigenic determinants, which are generated by a variety of environmental contact sensitizer (CS) chemicals associating with self-proteins to comprise these neo-antigens. In this issue of the European Journal of Immunology, Betts et al. [Eur. J. Immunol. 2017. 47: 1171-1180] provide intriguing data implying that common small molecule CSs such as dinitrochlorobenzene can also recruit and activate autoreactive CD1-restricted T cells specific for cell-endogenous lipids, which are enriched in human skin. The effects of dinitrochlorobenzene on CD1 T-cell recruitment and function were dependent on newly synthesized CD1 molecules and the presence of endogenous lipids. These findings shed new light on unanticipated mechanisms that have potential clinical relevance on a common and highly distressing disease state.
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Antígenos CD1/inmunología , Dermatitis por Contacto/inmunología , Lípidos/inmunología , Linfocitos T/inmunología , Animales , Presentación de Antígeno , Humanos , Ratones , Células T Asesinas Naturales/inmunologíaRESUMEN
Allergic contact dermatitis is a primarily T-cell-mediated inflammatory skin disease induced by exposure to small molecular-weight haptens, which covalently bind to proteins. The abundance of cutaneous T cells that recognize CD1a antigen-presenting molecules raises the possibility that MHC-independent antigen presentation may be relevant in some hapten-driven immune responses. Here we examine the ability of contact sensitizers to influence CD1-restricted immunity. Exposure of human antigen-presenting cells such as monocyte-derived dendritic cells and THP-1 cells to the prototypical contact sensitizer dinitrochlorobenzene potentiated the response of CD1a- and CD1d-autoreactive T cells, which released a vast array of cytokines in a CD1- and TCR-dependent manner. The potentiating effects of dinitrochlorobenzene depended upon newly synthesized CD1 molecules and the presence of endogenous stimulatory lipids. Further examination of a broad panel of contact sensitizers revealed 1,4-benzoquinone, resorcinol, isoeugenol, and cinnamaldehyde to activate the same type of CD1-restricted responses. These findings provide a basis for the antigen-specific activation of skin-associated CD1-restricted T cells by small molecules and may have implications for contact sensitizer-induced inflammatory skin diseases.
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Antígenos CD1/inmunología , Dermatitis por Contacto/inmunología , Células T Asesinas Naturales/inmunología , Linfocitos T/inmunología , Acroleína/análogos & derivados , Acroleína/farmacología , Presentación de Antígeno , Benzoquinonas/farmacología , Línea Celular , Células Dendríticas/inmunología , Dinitroclorobenceno/farmacología , Eugenol/análogos & derivados , Eugenol/farmacología , Humanos , Lípidos/inmunología , Activación de Linfocitos , Monocitos/efectos de los fármacos , Resorcinoles/farmacología , Piel/inmunologíaAsunto(s)
Linfocitos T CD8-positivos/inmunología , Proliferación Celular/efectos de los fármacos , Ciclopropanos/inmunología , Ciclopropanos/farmacología , Dermatitis Alérgica por Contacto/sangre , Técnicas In Vitro/métodos , Linfocitos T CD4-Positivos/inmunología , Humanos , Inmunidad Celular/efectos de los fármacos , Proyectos PilotoAsunto(s)
Antifúngicos/efectos adversos , Dermatitis Alérgica por Contacto/etiología , Erupciones por Medicamentos/etiología , Miconazol/análogos & derivados , Anciano , Diflucortolona/efectos adversos , Diflucortolona/análogos & derivados , Combinación de Medicamentos , Femenino , Humanos , Miconazol/efectos adversos , Tiña/tratamiento farmacológicoRESUMEN
BACKGROUND: Medical advances in the field of infection therapy have led to an increasing use of antibiotics, which, apart from eliminating pathogens, also partially eliminate naturally existing commensal bacteria. It has become increasingly clear that less exposure to microbiota early in life may contribute to the observed rise in "immune-mediated" diseases, including autoimmunity and allergy. OBJECTIVE: We sought to test whether the change of gut microbiota with the broad spectrum antibiotic enrofloxacin will modulate contact sensitivity (CS) in mice. METHODS: Natural gut microbiota were modified by oral treatment with enrofloxacin prior to sensitization with trinitrophenyl chloride followed by CS testing. Finally, adoptive cell transfers were performed to characterize the regulatory cells that are induced by microbiota modification. RESULTS: Oral treatment with enrofloxacin suppresses CS and production of anti-trinitrophenyl chloride IgG1 antibodies. Adoptive transfer experiments show that antibiotic administration favors induction of regulatory cells that suppress CS. Flow cytometry and adoptive transfer of purified cells show that antibiotic-induced suppression of CS is mediated by TCR αß+CD4+CD25+FoxP3+ Treg, CD19+B220+CD5+ IL-10+, IL-10+ Tr1, and IL-10+ TCR γδ+ cells. Treatment with the antibiotic induces dysbiosis characterized by increased proportion of Clostridium coccoides (cluster XIVa), C coccoides-Eubacterium rectale (cluster XIVab), Bacteroidetes, and Bifidobacterium spp, but decreased segmented filamentous bacteria. Transfer of antibiotic-modified gut microbiota inhibits CS, but this response can be restored through oral transfer of control gut bacteria to antibiotic-treated animals. CONCLUSIONS: Oral treatment with a broad spectrum antibiotic modifies gut microbiota composition and promotes anti-inflammatory response, suggesting that manipulation of gut microbiota can be a powerful tool to modulate the course of CS.
Asunto(s)
Antibacterianos/farmacología , Dermatitis por Contacto/inmunología , Fluoroquinolonas/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Traslado Adoptivo , Animales , Enrofloxacina , Ganglios Linfáticos/citología , Ratones Endogámicos C57BL , Bazo/citología , TrinitrobencenosRESUMEN
The objective of the study was to investigate the possibility of modulation of skin inflammation by topical treatment with a novel compound: an opioid-neurotensin hybrid peptide PK20 encompassing endomorphin-2 analog and modified fragment of neurotensin (8-13). Contact sensitivity response was induced in mice by skin sensitization with dinitrofluorobenzene (DNFB) followed by topical hapten application on ears. Mice were treated locally with PK20 or pure cream 2h after the challenge with DNFB. 2 and 24h after hapten exposure, ear thickness was determined. Ears were collected for histology and homogenization. Supernatants were used for measurement of contents of cytokines and lipid peroxidation products. Treatment with PK20 reduced significantly the late phase of contact sensitivity response, which was revealed by ear thickness diminution and reduction of inflammatory cell infiltration. The average concentrations of IL-1α, MCP-1, TNF-α and thiobarbituric acid-reactive substances were significantly decreased in the ears treated with the chimera in comparison to the control cream treated ears in DNFB sensitized/DNFB challenged group. We found that PK20 topical treatment alleviates hypersensitivity responses triggered by DNFB challenge and usage of the hybrid peptide may be a novel therapeutic strategy in the treatment of chronic inflammatory diseases. However, the mechanism remains unclear and needs further investigation.