Oral administration of lipoteichoic acid from Lactobacillus rhamnosus GG overcomes UVB-induced immunosuppression and impairs skin tumor growth in mice.

There is increasing evidence of the relevant connection and regulation between the gut and skin immune axis. In fact, oral administration of lipoteichoic acid (LTA) from Lactobacillus rhamnosus GG (LGG) prevents the development of UV-induced skin tumors in chronically exposed mice. Here we aim to evaluate whether this LTA is able to revert UV-induced immunosuppression as a mechanism involved in its anti-tumor effect and whether it has an immunotherapeutic effect against cutaneous squamous cell carcinoma. Using a mouse model of contact hypersensitivity, we demonstrate that LTA overcomes UV-induced skin immunosuppression. This effect was in part achieved by modulating the phenotype of lymph node resident dendritic cells (DC) and the homing of skin migratory DC. Importantly, oral LTA reduced significantly the growth of established skin tumors once UV radiation was discontinued, demonstrating that it has a therapeutic, besides the already demonstrated preventive antitumor effect. The data presented here strongly indicates that oral administration of LTA represents a promising immunotherapeutic approach for different conditions in which the skin immune system is compromised.

Occupational contact dermatitis in the wind energy industry.

BACKGROUND AND OBJECTIVES: In 2010, wind energy coverage in Spain increased by 16%, making the country the world's fourth largest producer in a fast-developing industry that is also a source of employment. Occupational skin diseases in this field have received little attention. The present study aims to describe the main characteristics of skin diseases affecting workers in the wind energy industry and the allergens involved. MATERIAL AND METHODS: We performed a descriptive, observational study of workers from the wind energy industry with suspected contact dermatitis who were referred to the occupational dermatology clinic of the National School of Occupational Medicine (Escuela Nacional de Medicina del Trabajo) between 2009 and 2011. We took both a clinical history and an occupational history, and patients underwent a physical examination and patch testing with the materials used in their work. RESULTS: We studied 10 workers (8 men, 2 women), with a mean age of 33.7 years. The main finding was dermatitis, which affected the face, eyelids, forearms, and hands. Sensitization to epoxy resins was detected in 4 workers, 1 of whom was also sensitized to epoxy curing agents. One worker was sensitized to bisphenol F resin but had a negative result with epoxy resin from the standard series. In the 5 remaining cases, the final diagnosis was irritant contact dermatitis due to fiberglass. CONCLUSIONS: Occupational skin diseases are increasingly common in the wind energy industry. The main allergens are epoxy resins. Fiberglass tends to produce irritation.

Anti-inflammatory effect of crude extract and isolated compounds from Baccharis illinita DC in acute skin inflammation.

UNLABELLED: ETHNOPHARMACOLOGYCAL RELEVANCE: The tea from the leaves of Baccharis illinita DC (Asteraceae family) is commonly used by the population as anti-inflammatory (including topically), protective gastric and anti-infectious. However, no studies have been done with this species to confirm its topical anti-inflammatory action. AIM: This study evaluated he topical effects of crude extract of leaves (CE) and its active constituents in 12-O-tetradecanoylphorbol acetate (TPA)-induced ear oedema. METHODOLOGY: CE and compounds effects were tested in commonly used models of TPA-, arachidonic acid (AA)- and capsaicin-ear oedema. Polymorphonuclear (PMN) cell migration was evaluated by mieloperoxidase and analyzed histologically. RESULTS: CE (0.1-1 mg/ear) caused a dose-related inhibition of TPA-induced ear oedema and PMN influx similarly to that produced by topical application of the steroidal anti-inflammatory drug dexamethasone. The active constituents of the AcOEt fraction kaurenoic acid, alpha-spinasterol, oleanolic acid and baurenol also inhibited TPA-induced ear edema. Histological analysis of the ear of CE-treated animals confirmed the reduction of edema and of PMN infiltration. Both CE and the nosteroidal anti-inflammatory drug indomethacin inhibited the AA-induced ear oedema, but did not change capsaicin-induced oedema. CONCLUSION: These results indicate that the CE and the active constituents have a topical anti-inflammatory effect and the possible mechanisms for the pharmacological effects are discussed.

Identification of the constituents of balsam of peru in tomatoes.

BACKGROUND: Studies show that balsam-restricted diets result in significant improvement of systemic contact dermatitis in patients with contact allergy to balsam of Peru (BOP). While tomatoes have been implicated as a frequent cause of BOP-related dermatitis, the presence of BOP in tomatoes has never been confirmed. OBJECTIVES: High-performance liquid chromatography coupled with mass spectrometry (liquid chromatography [LC]-MS) and UV spectrometry (LC-UV) was used to detect the possible presence of BOP constituents in tomatoes. METHODS: Samples of beefsteak, cherry, and plum tomatoes were extracted in ethyl acetate and analyzed with LC-MS and LC-UV for the presence of the following sensitizing constituents of BOP: benzoic acid, benzyl alcohol, trans-cinnamic acid, cinnamic alcohol, cinnamyl cinnamate, coniferyl alcohol, eugenol, isoeugenol, and methyl cinnamate. RESULTS: The initial LC-MS analysis of each tomato extract showed multiple peaks. Two of these peaks had molecular weights of 134 and 180, which correspond to cinnamic alcohol and coniferyl alcohol, respectively. The analysis did not show peaks corresponding to the molecular weights of the remaining compounds. Cochromatography of tomato extract with cinnamic alcohol and coniferyl alcohol using LC-UV further suggested the presence of these compounds in the tomato extract. CONCLUSION: Coniferyl alcohol and cinnamic alcohol, constituents of BOP, are present in beefsteak, cherry, and plum tomatoes.

Contact hypersensitivity to stainless steel cages (chromium metal) in hairless descendants of mexican hairless dogs.

Canine allergic contact hypersensitivity is an uncommon skin disease as compared with human beings because hair coat is a good natural barrier to environmental contactants. In our colony of hairless dogs housed in stainless steel cages, we have encountered spontaneously occurring contact hypersensitivity. The author has attempted to study the toxicological effects of environmental sensitizing substances on the canine skin. The purpose of this study is to elucidate dermatological characteristics in canine species with contact hypersensitivity. This skin lesion was investigated by patch tests, macroscopic observations, and histopathological examinations. Patch tests exhibited positive reactions to potassium dichromate. Macroscopically, early lesions were macules and/or papules and they gradually progressed to severe inflammatory dermatitis over the dorsum. In the chronic phase, lichenification, kyperkeratosis, hyperpigmentation, dryness, scaliness, and fissuring were observed in the skin. Avoidance of contact with the stainless steel cages resulted in clinical improvement. Histopathologically, the epidermis apparently showed hyperkeratosis, thickening, hyperplasia, and rete ridge formation. Lichenified lesions had clumps of melanin granules in the stratum basale and spinosum. In the dermis, there was marked edema and dense mononuclear cell infiltration. Vasodilation, hemorrhage, and hyperplasia of sebaceous glands were also found. Both dermal mast cells and epidermal Langerhans cells significantly increased in the skin lesions, as compared with nonlesional sites. The present results revealed that constant contact with stainless steel cages (chromium metal) caused contact hypersensitivity in hairless dogs with very sparse hairs.

Invariant NKT cells rapidly activated via immunization with diverse contact antigens collaborate in vitro with B-1 cells to initiate contact sensitivity.

In cutaneous contact sensitivity there is an early elicited innate cascade of complement, mast cells, and platelets activated via IgM Abs. This response is required to initiate the elicitation of acquired classical contact sensitivity by leading to local recruitment of effector T cells. We recently performed in vivo experiments showing that collaboration is required between innate-like invariant Valpha14+ NKT cells (iNKT) and the innate-like B-1 B cell subset to induce this initiation process. Contact sensitization triggers iNKT cells to produce IL-4 to coactivate the B-1 cells along with specific Ag for production of the initiating IgM Abs. We now describe in vitro collaboration of iNKT and B-1 cells. Normal peritoneal B-1 cells, incubated in vitro with soluble Ag, and with 1-h in vivo immune iNKT cells producing IL-4, are activated to mediate the contact sensitivity-initiation cascade. The three components of this process can be activated by different Ag. Thus, 1-h iNKT cell activation, B-1 cell stimulation, and generation of immune effector T cells can be induced by sensitization with three different Ag to respectively generate IL-4 and Ag-specific IgM Abs, to recruit the Ag-specific effector T cells. These findings have relevance to allergic and autoimmune diseases in which infections can trigger exacerbation of T cell responses to allergens or to autoantigens.

[Immunological mechanisms in contact dermatitis]. / Mecanismos inmunológicos en la dermatitis de contacto.

Contact dermatitis is an altered state of skin reactivity induced by the exposure to an external antigen which begins a series of mechanisms where Langerhans cells and keratinocytes play an important role in antigen presentation and have an effective response by chemokines, interleukins and lymphocytes T.

Effects of neurointermediate pituitary lobectomy on humoral and cell-mediated immune responses in the rat.

OBJECTIVE: Chronic stress is characterized by an increased activity of the hypothalamic-pituitary-adrenocortical axis and decreased humoral and cell-mediated immune responses. In the rat, corticosterone is the principal natural immune suppressor. Neurointermediate pituitary lobectomy (NIL) in rats induces diabetes insipidus and protracted increases in basal adrenocorticotropin and corticosterone plasma levels, a situation that resembles chronic stress. In this paper, we evaluated the effects of NIL on humoral (hemagglutinin titers and footpad swelling to sheep red blood cells--SRBC) and cell-mediated immune responses (contact hypersensitivity to dinitrochlorobenzene). METHODS: The studies were conducted on NIL Wistar rats (body weight 150-200 g) 3 weeks after surgery. For comparisons, nonoperated control rats were used. RESULTS: NIL resulted in an increased water intake. Body weight gain and adrenal, thymus, and spleen weights were within the range of nonoperated controls. Eight days after SRBC immunizations a second SRBC injection into the footpad resulted in a decreased swelling response in NIL rats. The hemagglutinin titers were also reduced in the NIL rats. CONCLUSIONS: These results indicate that: (1) NIL reduces humoral immune responses and decreases the cell-mediated immune response; (2) the immune alterations are most likely due to the increased activity of the hypothalamic-pituitary-adrenocortical axis induced by NIL, and (3) NIL animals constitute a valuable paradigm to study hypothalamic-pituitary-immune interactions.

Eosinophil recruitment into sites of delayed-type hypersensitivity reactions in mice.

The selective accumulation of eosinophils in tissue is a characteristic feature of allergic diseases where there is a predominance of lymphocytes expressing a Th2 phenotype. In an attempt to define factors determining specific eosinophil accumulation in vivo, we have used a radiolabeled technique to assess the occurrence and the mechanisms underlying (111)In-eosinophil recruitment into Th1- and Th2-predominant, delayed-type hypersensitivity (DTH) reactions. Eosinophils were purified from the blood of IL-5 transgenic mice, labeled with (111)In and injected into nontransgenic CBA/Ca mice. Th1- and Th2-predominant, DTH reactions were induced in mice by immunization with methylated bovine serum albumin (MBSA) in Freund's complete adjuvant or with Schistosoma mansoni eggs, respectively. In these animals, (111)In-eosinophils were recruited in skin sites in an antigen-, time-, and concentration-dependent manner. Depletion of CD4+ lymphocytes abrogated (111)In-eosinophil recruitment in both reactions. Pretreatment of animals with anti-IFN-gamma mAb abrogated (111)In-eosinophil recruitment in MBSA-immunized and -challenged animals, whereas anti-IL-4 inhibited (111)In-eosinophil recruitment in both models. Local pretreatment with an anti-eotaxin polyclonal antibody inhibited the MBSA and SEA reactions by 51% and 39%, respectively. These results demonstrate that, although eosinophilia is not a feature of Th1-predominant, DTH reactions, these reactions produce the necessary chemoattractants and express the necessary cell adhesion molecules for eosinophil migration. The control of the circulating levels of eosinophils appears to be a most important strategy in determining tissue eosinophilia.

Determination of Blomia tropicalis-specific IgE and IgG subclasses in atopic dermatitis patients.

BACKGROUND: To verify the importance of Blomia tropicalis in atopic dermatitis (AD), we determined the cutaneous reactivity and the serum level of B. tropicalis-specific IgE and IgG subclasses in AD patients. METHODS: B. tropicalis-specific IgE and IgG subclasses were determined in AD patients and compared with bronchial asthma (BA) patients and a control group (CG) of nonatopic subjects. Specific IgE was obtained by skin prick test and RAST. B. tropicalis-specific IgG subclasses were determined by ELISA. The data were statistically analyzed by chi-square test (Mantel-Haenszel) and odds ratio (OR). RESULTS: We detected positive skin prick tests in 61.76% of AD and 83.33% of BA patients, and in 12.5% of the CG. RAST was positive in 44.12% of AD and in 61.90% of BA patients, but not in the CG. B. tropicalis-specific IgG1 and IgG2 subclasses showed no significant differences between the three groups. IgG3 subclass positivity was statistically significant in AD patients (41.17%) when compared to BA patients (14.29%) and the CG (16.67%). The determination of B. tropicalis-specific IgG4 was positive in 32.35% of AD patients, 21.43% of BA patients, and 8.33% of the CG. CONCLUSIONS: These results confirm that the storage mite B. tropicalis is an important allergen in AD. It is possible that IgG3 activates the complement in AD patients, releasing vasoactive amines that further amplify the allergic reaction. The positive results of the B. tropicalis-specific IgG4 found in AD and BA were probably due to chronic exposure to this storage mite in the home environment.

CD8+ T cells are the effectors of the contact dermatitis induced by urushiol in mice and are regulated by CD4+ T cells.

BACKGROUND: The exposure of human skin to leaves and branches of litre (Lithraea caustica), a Chilean endemic tree, induces a severe contact dermatitis characterized by swelling and pruritus in susceptible individuals. The allergenic priniciple of litre is 3-pentadecyl (10-enyl) catechol (litreol), which is structurally similar to the allergens isolated from poison oak and poison ivy. All of them belong to a family of compounds named urushiols. As a proelectrophilic allergen, litreol must be intracellularly activated before modifying proteins of individuals exposed to it. As a result, self-peptides derived from litreol-modified intracellular proteins would be presented in the context of class I MHC molecules. We hypothesized that CD8+ T lymphocytes would play a major role during the effector phase of the immune response induced by those modified peptides. In order to test this hypothesis, we investigated the cellular immune response to litreol in Balb/cJ mice. The role of the different lymphocyte subpopulations in this response was assessed by immunodepleting mice of CD4+ or CD8+ T lymphocytes using specific monoclonal antibodies (mAbs). We report the observation that the contact dermatitis induced by litreol has two components: a primary response which does not require TCRalpha beta+ T cells, and a secondary response mediated mainly by CD8+ T cells and regulated by CD4+ T cells. Our results show that CD8+ lymphocytes play a central role as effectors of the secondary response to litreol. Furthermore, our data suggest that two functionally different CD4+ T subpopulations serve as regulators of the CD8+ T cell function: a CD4+ T helper population sensitive to a low dose of the depleting mAb, and CD4+ T suppressor population which is eliminated only with a high dose of depleting mAb.

T cells and the skin

In addition to its role as a mechanical barrier, the skin plays an important role in temperature regulation, vitamin D synthesis and absorption of ultraviolet radiation. The importance of the skin as an immunological organ was not fully appreciated until the advent of immunosuppressive agents such as cyclosporin and tacrolimus, which have a predominant action against T lymphocytes and have been found to be effective in the management of common skin diseases such as atopic eczema and psoriasis. T lymphocytes are of fundamental importance to the immune system. Access from the vascular compartment into the skin is facilitated by adhesion molecules located on the endothelial of dermal blood vessels. Selective upregulation of adhesion molecules occurs in various inflammatory skin diseases and specific skin homing T lymphocytes preferentially enter the skin rather than other organs. T cell have recently been classified into Th1 and Th2 cells based on their cytokine profile. Th1 cells produce interleukin 2 (IL-2) and interferon gamma, important in macrophage activation and cytotoxity, and Th2 cells produce IL-4 and IL-5, important in B cell maturation and humoral immunity. Contact dermatitis and psoriasis are characterised by Th1 cells and atopic dermatitis by Th2 cells. The Th1/Th2 profile is also important in infectious diseases such as leprosy in which polarisation towards tuberculoid or lepromatous disease depends on a predominance of Th1 or Th2 cells, respectively. Future management of diseases affecting the skin is likely to depend on a greater understanding of the infiltrating T cell subsets and appropriate modulation of the Th1 and Th2 profile.(AU)

Potencial de sensibilizaçäo cutânea de duas formulaçöes de um creme básico em pacientes com dermatoses alérgicas / Skin sensitization potential of two formulas of a basic cream in patients with allergic dermatoses

Objetivos. Avaliar se a formulação de um crème básico cosmético (Crème Universal© acrescida de uma essência A ou B aumentaria o potencial de sensibilização em uma população suscetível. Métodos: Estudo multicêntrico, comparativo, simples-cego, randomizado, conduzido em 179 pacientes adultos portadores de pele xerótica e dermatite de contato e/ou atópica, distribuídos em 2 grupos parcelados A e B que utilizaram crème com essência A ou B respectivamente. Após 14 dias de uso contínuo de crème todos os pacientes foram submetidos a teste de contato com uma bateria padrão e mais os componentes do crème. Resultados: O teste de contato foi positivo para algum dos componentes do crème em apenas três (1,7 por cento) casos do total de pacientes e o índice geral de reação adversa foi de 8 por cento no Grupo A e 7,6 por cento no Grupo B. Não houve diferença estatisticamente significantes entre os dois grupos. Conlusão: A utilização do Crème Universal© associado a uma essência A ou B resultou num índice de sensibilização extremamente baixo numa população especialmente susceptível. Não houve diferença de reações com o acréscimo de essência A ou B.

Pruebas cutáneas a diferentes especies de ácaros en niños asmaticos de la Ciudad de México / A comparative study of effects adverse a contrast ionic iodine in preventive medication

Con la finalidad de deterctar la sensibilidad a otras especies de ácaros, además de Dermatophagoides farine (Df), Dermatophagoides pteronyssinus (Dp) se realizaron pruebas cutáneas a cien niños habitantes de la Ciudad de México. Estas se hicieron en la cara anterior de antebrazos, mediante Multitest con extractos glicerinados. Fueron 34 niñas y 66 niños, entre cuatro y 14 años de edad (promedio de 9.1), con historia de asma leve o moderada, de dos meses a 12 años de evolución, Dp resultó positivo en 96, Df en 80, Euroglyphus maynei en 41, Chortoplyphus en 22 Blomia tropicalis en 17, Tyrophagus putrescentiae y Glycyphagus en 12, Acarus siro, Lepidoglyphus destructor y Gophieria en 7. La hipersensibilidad a todas las especies fue común. A pesar de saberse que existe reacción cruzada entre especies, se han encontrado alergenos específicos de especie, lo que podría dar importancia clínica a estos diagnósticos y sus tratamientos