Potential classification of chemical immunologic response based on gene expression profiles.

Occupational immune diseases are a serious public health burden and are often a result of exposure to low molecular weight (LMW) chemicals. The complete immunological mechanisms driving these responses are not fully understood which has made the classification of chemical allergens difficult. Antimicrobials are a large group of immunologically-diverse LMW agents. In these studies, mice were dermally exposed to representative antimicrobial chemicals (sensitizers: didecyldimethylammonium chloride (DDAC), ortho-phthalaldehyde (OPA), irritants: benzal-konium chloride (BAC), and adjuvant: triclosan (TCS)) and the mRNA expression of cytokines and cellular mediators was evaluated using real-time qPCR in various tissues over a 7-days period. All antimicrobials caused increases in the mRNA expression of the danger signals Tslp (skin), and S100a8 (skin, blood, lung). Expression of the TH2 cytokine Il4 peaked at different timepoints for the chemicals based on exposure duration. Unique expression profiles were identified for OPA (Il10 in lymph node, Il4 and Il13 in lung) and TCS (Tlr4 in skin). Additionally, all chemicals except OPA induced decreased expression of the cellular adhesion molecule Ecad. Overall, the results from these studies suggest that unique gene expression profiles are implicated following dermal exposure to various antimicrobial agents, warranting the need for additional studies. In order to advance the development of preventative and therapeutic strategies to combat immunological disease, underlying mechanisms of antimicrobial-induced immunomodulation must be fully understood. This understanding will aid in the development of more effective methods to screen for chemical toxicity, and may potentially lead to more effective treatment strategies for those suffering from immune diseases.

Indirubin, a purple 3,2- bisindole, inhibited allergic contact dermatitis via regulating T helper (Th)-mediated immune system in DNCB-induced model.

ETHNOPHARMACOLOGICAL RELEVANCE: Indirubin, isolated from Indigo naturalis (Apiaceae) is a purple 3,2- bisindole and a stable isomer of indigo. Although it is known to have anti-inflammatory activities, its mechanism of action has not been elucidated. MATERIALS AND METHODS: Seven-week-old female BALB/c mice were sensitized with 1-chloro-2,4-dinitrobenzene (DNCB) to induce skin inflammation. Hematoxylin and eosin staining was performed to assess epidermal and dermal hyperplasia, which were determined by measuring the thicknesses of the epidermis and dermis, respectively. We also evaluated serum immunoglobulin E (IgE) levels and cytokines production, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, 6 and Interferon (IFN)-gamma. In addition, we investigated nuclear factor (NF)-κB, IκB-α and mitogen-activated protein (MAP) kinase activities for verifying the molecular mechanism of inflammation. RESULTS: Indirubin treatment suppressed skin inflammation in DNCB-exposed mice. The skin lesions were significantly thinner in the Indirubin-treated group than in untreated controls, and the hyperkeratosis disappeared. Indirubin reduced the total serum IgE level and cytokines production. In addition, it normalized NF-κB, IκB-α and MAP kinase expression. CONCLUSIONS: Indirubin might be a useful treatment for allergic contact dermatitis via regulating the co-expression of T helper (Th) 1 and 2 cell-mediated immune responses.

Immunomodulatory effect of Eriobotrya japonica seed extract on allergic dermatitis rats.

We examined the immunomodulatory effect of Eriobotrya japonica seed extract (ESE) on rat allergic dermatitis elicited by repeated dinitrofluorobenzene (DNFB) application on the ear. Oral administration of ESE significantly inhibited development of allergic dermatitis based on lower ear thickness and serum immunoglobulin E (IgE) levels. Th1 cytokine interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), Th2 cytokine interleukin-4 (IL-4) and interleukin-10 (IL-10) in the lesional skin were determined. Oral administration of ESE significantly decreased IL-4 while significantly increasing IL-10 in lesional skin, and the lower levels of IFN-gamma and IL-2 were reversed by oral administration of ESE. The infiltration of eosinophils in the lesional skin was decreased by oral administration of ESE. These results suggested that ESE exerts anti-allergic actions by improving the balance of Th1/Th2 in allergic dermatitis.

Role of four major components in the effect of Si-Ni-San, a traditional Chinese prescription, against contact sensitivity in mice.

Previously, we demonstrated the inhibitory effects of Si-Ni-San, a traditional Chinese prescription, on picryl chloride-induced ear contact sensitivity (PCl-CS). This study aimed to evaluate the role of the four major constituents contained in the prescription (saikosaponins, paeoniflorin, naringin and glycyrrhizin) in the inhibitory effect. When administered during the induction phase, saikosaponin a and glycyrrhizin showed significant inhibitory effects, while paeoniflorin and naringin did not. These components in Si-Ni-San also inhibited the activation and proliferation of T lymphocytes as well as the production of cytokines such as tumour necrosis factor-alpha and interferon-gamma to different extents. Saikosaponin a and paeoniflorin dose-dependently reduced the splenocyte adhesion to type I collagen, while glycyrrhizin only showed a slight tendency. Furthermore, treatment with glycyrrhizin or saikosaponin a, rather than paeoniflorin or naringin, moderately inhibited the matrix metalloproteinase (MMP)-2 activity of the splenocytes from PCl-CS mice, and the combination of all four components showed a strong inhibition against MMP-2. Moreover, the components markedly decreased the serum level of nitric oxide in PCl-sensitized mice. The results indicated that saikosaponin a and glycyrrhizin may be the major contributors in the alleviation effect of Si-Ni-San on contact sensitivity, and paeoniflorin and naringin may exhibit a co-operative effect.

[Il-10 expression is involved in the regulation of the immune response by omega 3 fatty acids]. / La expresión de IL-10 interviene en la regulación de la respuesta inflamatoria por los acidos grasos omega 3.

INTRODUCTION: Polyunsaturated fatty acids play a key role in a huge number of biological functions. Western diets are highly rich in w-6 fatty acids. However the content of w-3 fatty acids is not suitable in those diets, despite of their importance in normal development of the human body and regulation of immune response. The aim of this work is to examine the effect of w-3 fatty acids enriched diet in the regulation of inflammatory response. MATERIAL AND METHODS: Balb/c mice were fed either w-6 fatty acids rich diet (100% sunflower oil) or w-3 fatty acids fortified diet (12% fish oil plus 88% sunflower oil) during 28 days. Twelve hours prior to sacrifice, the mice were treated with 2,4-ninitro-1-fluorobezene on the left ear to induce the inflammatory reaction. Afterwards the mice were sacrificed and the different samples collected were analized. RESULTS: Ear inflammation of mice fed the w-3 diet was significantly lower. Leukocyte infiltration and oxidative stress were also lower in those mice. To explain these results, cytokine expression and plasma eicosanoid concentration were measured. An increase in IL-10 levels and a down regulation of Th1 and Th2 responses were observed in mice fed the w-3 diet. CONCLUSION: Not only n-3 fatty acids exerts an antiinflammatory and an antialergical role but also they enhance some of the organism defenses. Our data suggest that w-3 fatty acids downregulate the inflammatory response by enhancing IL10 expression.

Season of birth as predictor of atopic manifestations.

The relation between month of birth, sensitisation, and manifestations of atopy was assessed in 209 children who were followed from birth to 12-15 years. Children born during the tree pollen season were less likely to develop allergic rhinoconjunctivitis, IgE antibodies to pollen, or a positive screening test for IgE antibodies (odds ratio 0.28, 0.41, 0.35, respectively) than children born during the rest of the year. The prevalence of IgE antibodies to food and animal dander at 9 months and to atopic disease was higher in children born in the autumn and winter, that is, September to February, compared to the spring and summer (egg 20% v 6%; milk 10% v 2%). Thus sensitisation to pollen and allergic rhinoconjunctivitis is least common in children born in the spring, while birth in September to February is associated with an increased incidence of sensitisation to food and of atopic disease.