Eosinophil hypersegmentation is a possible marker to monitor the disease activity of atopic dermatitis

BackgroundIn the present study, we tried to clarify whether nuclear hypersegmentation of peripheral blood eosinophils is correlated with peripheral eosinophil counts and/or the activity of atopic dermatitis (AD) in 79 patients.MethodsWe also compared the grades of skin scores, peripheral eosinophil counts, the rate of hypersegmentation of eosinophils and serum eosinophil cationic protein (ECP) concentrations in eight patients before and after treatment.ResultsThere was a positive correlation between the skin scores of AD and peripheral eosinophil counts (P < 0.01), between the skin scores of AD and the number of nuclear lobes of eosinophils (P < 0.01) and between eosinophil counts and the number of nuclear lobes of eosinophils when the number of nuclear lobes of eosinophils was fewer than three (P < 0.01). A positive correlation was observed between serum ECP concentrations and eosinophil counts and/or skin scores of AD (P < 0.001). A negative correlation was observed between serum ECP concentrations and the number of nuclear lobes fewer than two (P < 0.05). During therapy, peripheral eosinophil counts and the degree of hypersegmented eosinophils decreased significantly, and this was associated with recovery of skin conditions, but not with serum ECP concentrations.ConclusionsThese results suggest that eosinophil hypersegmentation may reflect activated eosinophils and also that the observation of nuclear hypersegmentation in peripheral blood eosinophils is useful to recognize the disease activity of AD.     

Urinary eosinophil-derived neurotoxin concentrations in patients with atopic dermatitis: a useful clinical marker for disease activity.

BACKGROUND: It has been reported that measurements of eosinophil-derived neurotoxin (EDN) may be useful for identifying eosinophil activities in allergic diseases including atopic dermatitis. METHODS: EDN concentrations in the urine were measured by enzyme-linked immunosorbent assay, and the number of eosinophils in the peripheral blood was counted in 30 patients with atopic dermatitis. The severity of atopic dermatitis was graded on the criteria proposed by Rajka and Langeland. The disease activity was assessed by each patient on a visual analogue scale (VAS). RESULTS: Urinary concentrations of EDN in patients with atopic dermatitis showed a significant positive correlation with disease severity. Urine EDN concentrations also correlated with VAS scores for itching, skin condition, overall skin symptoms and total VAS score, but not with the VAS score for skin dryness. Urinary EDN concentrations did not correlate with the number of eosinophils in the peripheral blood. CONCLUSIONS: The urinary EDN concentration in patients with atopic dermatitis is a useful clinical marker for monitoring disease activity.     

Airway inflammation and basement membrane tenascin in newly diagnosed atopic and nonatopic asthma

Previous studies have shown both similar and distinct inflammatory changes in atopic and nonatopic asthma. This study was set to investigate the bronchial inflammatory cell infiltrate and subepithelial basement membrane (BM) tenascin deposition in subjects with newly diagnosed asthma and bronchial hyperresponsiveness (BHR). Seventy-nine asthmatic subjects (age 18-60 years) were recruited and 58 were atopic according to skin prick testing. The patients recorded asthma symptoms and peak flow measurements for 14 days. Lung function and BHR were measured by spirometry and histamine challenge. Serum eosinophil cationic protein (ECP) and blood eosinophils were assessed. Fiberoptic bronchoscopy was performed to obtain bronchial biopsies. Serum ECP was higher in the atopic group but eosinophil counts did not differ. There were no differences in inflammatory cells studied (activated eosinophils, T-lymphocytes, mast cells or macrophages) between nonatopic and atopic subjects. BM tenascin layer was significantly thicker in atopic compared with nonatopic subjects (7.6 vs 6.3 microm, P = 0.007). The thickness of tenascin correlated with eosinophil, T-lymphocyte, and macrophage counts, as well as with IL-4-positive cell counts and the correlation was seen only in atopic asthmatics. These findings suggest that inflammatory cells may have a regulatory role in tenascin expression in atopic asthma.     

An improved mouse model of atopic dermatitis and suppression of skin lesions by an inhibitor of Tec family kinases.

Background: Atopic dermatitis is a chronic or chronically relapsing, pruritic inflammatory skin disease. The incidence of atopic dermatitis has dramatically increased during the past three decades in industrialized countries. We attempted to develop an improved method to induce an animal model of atopic dermatitis and to use it to evaluate the efficacy of a Tec family kinase inhibitor. Methods: We treated dermatitis-prone inbred mice, NC/Nga, by repetitive epicutaneous applications of a house dust mite allergen and staphylococcal enterotoxin B to induce atopic dermatitis-like skin lesions. Results: We established a highly efficient protocol to induce skin lesions in NC/Nga mice, which were histologically and immunologically similar to human atopic dermatitis. Similar to human patients, serum IgE levels were increased in dermatitis-induced mice. Consistent with the proposed roles of infiltrated immune cells in the pathogenesis of human atopic dermatitis, skin lesions were treatable with terreic acid, an inhibitor of Tec family kinases, as well as dexamethasone. Conclusions: We established a highly efficient, highly reproducible protocol to induce skin lesions in NC/Nga mice and successfully applied it to show the efficacy of terreic acid in treating skin lesions. This mouse model of atopic dermatitis will be useful to study the pathogenetic processes of atopic dermatitis and to evaluate the efficacy of drug candidates.     

Chemokine networks in atopic dermatitis: traffic signals of disease

Atopic dermatitis is a chronic or chronically relapsing inflammatory skin disease with a prevalence ranging from 10% to 20% in children and 1% to 3% in adults of developed countries. Skin-infiltrating leukocytes play a pivotal role in the initiation and amplification of atopic skin inflammation. Recent studies demonstrated that infiltration of inflammatory cells into tissues is regulated by chemokines. A subset of chemokines including CCL27, CCL17, CCL22, CCL18, CCL11, and CCL13 are highly expressed in atopic dermatitis. The corresponding chemokine receptors are found on the main leukocyte subsets involved in allergic skin inflammation, such as T cells, eosinophils, and dendritic cells. In this article, we provide an overview of the role of chemokines in the complex immunopathogenesis of atopic dermatitis, highlighting potential areas for therapeutic intervention.     

Eosinophil granule proteins in serum and urine of patients with helminth infections and atopic dermatitis

Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EPX) are cytotoxic molecules involved in helminth infections and allergic reactions. Hitherto most clinical chemical studies have been concerned with the analysis of serum ECP in allergic diseases. The aim of this study was to examine whether serum as well as urine levels of these proteins are useful clinical chemical parameters in helminthiases and allergic diseases such as atopic dermatitis. Comparing these diseases under the same methodological conditions, levels of ECP and EPX were generally higher in helminthiases than in atopic dermatitis and non-helminth, non-allergic diseases. The highest levels of both proteins occurred in tropical worm diseases, in particular hookworm disease and onchocerciasis. When comparing helminthiases with allergic disorder, only hookworm disease (ECP and EPX) and onchocerciasis (EPX) exhibited significantly higher eosinophil cationic protein serum levels than atopic dermatitis. In patients with schistosomiasis mansoni and egg loads of > 1000-10 000 eggs/g stool (epg) EPX serum levels were significantly higher than in patients exhibiting loads < 1000 epg. Urinary analyses revealed only EPX to be present in measurable amounts. Levels of this protein were much higher in urine of patients with hookworm disease and onchocerciasis than in those with atopic dermatitis and in healthy controls. The results suggest that besides serum EPX, urinary EPX may be a useful clinical chemical parameter in eosinophilia of helminth and allergic aetiology.     

Patch tests in the diagnosis of food allergies in the nursing infant

The atopy patch-test has been shown to be useful in diagnosis of delayed reactions in infants with atopic dermatitis or digestive symptoms. The combination of skin prick testing and patch testing can significantly enhance the accuracy in diagnosis of specific food allergy in infants with atopic dermatitis or digestive symptoms.     

Serum eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in childhood asthma: The influence of atopy

The purpose of this study was to determine the value of serum measurements of eosinophil cationic protein (ECP) and eosinophil protein X (EPX) in diagnosing asthma in children, and to investigate the influence of concomitant allergic diseases and atopic sensitization, assessed by skin prick tests (SPT), on these markers. ECP and EPX were determined in 36 children with asthma, in 33 children with other symptoms from lower airways disease (OSLA), and in 166 control children. Sixteen children with asthma but no anti-inflammatory therapy had significantly higher concentrations of ECP and EPX (ECP: 27.5 μg/L, P < 0.001; EPX: 59.9 μg/L, P < 0.001) than the control children (ECP: 11.2 μg/L; EPX: 26.2 μg/L). In the 20 children on anti-inflammatory therapy, ECP values were similar to those of controls. The children with OSLA (ECP: 13.6 μg/L, P < 0.01; EPX: 47.2 μg/L, P < 0.001) differed significantly from controls. When using the value of 24.7 μg/L (97.5 percentile in the 68 non-atopic controls) as a pathologic upper limit for ECP, 10 (63%) of the 16 asthmatic children on no maintenance medication, two (10%) of the 20 asthmatics on maintenance therapy, and 11 (33%) of the 33 children with OSLA had high ECP; the same figure was only 18 (11%) in the 166 control children. Both ECP and EPX had a significant association with allergic disorders and with SPT reactivity. In multivariate logistic regression analysis, an elevated ECP was significantly associated with asthma (OR 2.3, 95%Cl 1.1–4.9) and atopic dermatitis (2.9, 1.2–6.9), and an elevated EPX was significantly associated with asthma (2.61, 1.19–5.74) and allergic rhinoconjunctivitis (5.23, 1.46–18.73). We conclude that serum concentrations of both ECP and EPX are higher in asthmatic than in healthy children. However, other allergic diseases, such as allergic rhinoconjunctivitis, atopic dermatitis, and allergic skin sensitization also raise the concentrations of these markers. This limits their usefulness in the diagnosis of childhood asthma. Pediatr. Pulmonol. 1998; 25:167–174. © 1998 Wiley-Liss, Inc.     

A novel atopic dermatitis model induced by topical application with dermatophagoides farinae extract in NC/Nga mice.

BACKGROUND: Atopic dermatitis is a chronically relapsing inflammatory skin disease. Animal models induced by relevant allergens play a very important role in the elucidation of the disease. The patients with atopic dermatitis are highly sensitized with mite allergens such as Dermatophagoides farinae (Df). Therefore, in the present study, we tried to develop a novel model for atopic dermatitis by repeated application with Df extract ointment. METHODS: Df extract ointment was repeatedly applied to the back of NC/Nga mice together with barrier disruption. Atopic dermatitis-like skin lesions were evaluated by dermatitis scores, skin histology and immunological parameters. The effect of corticosteroid and calcineurin inhibitor was also examined. RESULTS: Repeated application of Df extract ointment caused rapid increase in dermatitis scores. Clinical (skin dryness, erythema, edema and erosion) and histological symptoms (dermal and epidermal thickening, hyperkeratosis, parakeratosis and inflammatory cell infiltration) in this model were very similar to those in human atopic dermatitis. Serum total and Df-specific IgE levels were elevated in this model compared with normal mice, and draining lymph node cells isolated from the mice that exhibited dermatitis produced significant amounts of interleukin-5, interleukin-13 and interferon-gamma after re-stimulation with Df. Furthermore, current first-line drugs for the treatment of human atopic dermatitis, corticosteroid and tacrolimus ointments, were effective against the clinical and histological symptoms in this model. CONCLUSIONS: These results suggest that the model we have established is useful for not only elucidating the pathogenesis of atopic dermatitis but also for evaluating therapeutic agents.     

Effect of extensively hydrolyzed milk formula on growth and resistance to bronchitis and atopic dermatitis in infants and toddlers.

OBJECTIVE: This study aimed to evaluate the adverse effects of extensively hydrolyzed milk formula on growth in infants and toddlers. METHODS: Prospectively, 45 infants and toddlers with a positive history of cow's milk allergy confirmed by positive skin prick test and high IgE levels for either alpha-lactalbumin, beta-lactoglobulin, or casein and positive single-blind food challenge received extensively hydrolyzed milk formulas for 1 year. Sex-normalized percentiles of heights and weights of infants and toddlers before their enrollment in the study were compared to those at the end of the study. The contribution of breastfeeding, early use of bottle feeding and intake of adapted or special milk formulas, and history of bronchitis and atopic dermatitis on toddlers' growth were also evaluated by multivariate analysis. RESULTS: Similar percentiles of the children's weight and height were observed at the beginning of the study and 1 year later. According to the multivariate analysis, sex, breastfeeding, early bottle feeding, ingestion of adapted or special milk formulas, atopic dermatitis, and bronchitis were not correlated with either the children's weight or height at diagnosis of the allergy or at 1 year of follow-up (P > .10). Weights and heights were not different between toddlers who had atopic dermatitis or bronchitis during the study period and those who did not. CONCLUSIONS: Growth of infants and toddlers with cow's milk allergy was not affected by the intake of extensively hydrolyzed milk for 1 year. Atopic dermatitis and bronchitis did not appear to have any deleterious effect on these children's growth.     

Risk of allergy to food proteins in topical medicinal agents and cosmetics

The risk of allergy to food proteins in cosmetics and topical medicinal agents is poorly evaluated. IgE dependent contact urticaria and contact dermatitis are observed. Eleven cases (7 infants and 4 women) are reported. Wheat, egg, oats, milk, peanut proteins are incriminated by prick-tests or atopy patch-tests. Cases are related to a previous food allergy and other ones may indicate primary sensitization to topical creams mainly used for skin care of atopic dermatitis. A consecutive exercise induced anaphylaxis to wheat and a long lasting sensitization to wheat have been observed. A clear and accurate identification of food allergens in cosmetics and topical agents is necessary. Given the hyper-permeability of infant skin, topical products containing food proteins of known allergenicity are contra-indicated for neonates, and for infants with atopic dermatitis, which may be associated with skin hyper-permeability.     

Effects of Suplatast Tosilate on Airway Inflammation and Airway Hyperresponsiveness

Suplatast tosilate (IPD®) is a Th2 cytokine inhibitor that lowers the titer of the IgE antibody through specific inhibition of the production of IL (interleukin)-4 and IL-5 by T cells and inhibits tissue infiltration by eosinophils. In this clinical trial, suplatast tosilate (300 mg/day) was administered orally for 4 weeks to 25 patients (13 patients with atopic asthma, 12 patients with nonatopic asthma) whose bronchial asthma was staged in step 1 or step 2 according to the Guidelines for Prevention and Management of Bronchial Asthma, 1998. Before and after administration, the parameters of airway inflammation, that is, peripheral blood eosinophils count, serum level of eosinophil cationic protein (ECP), ECP level in induced sputum, airway hyperresponsiveness (D_min), and morning peak expiratory flow (PEF), were measured. The peripheral blood eosinophil count, serum level of ECP, and ECP level in induced sputum decreased significantly. Of these parameters, the ECP level in induced sputum was the most sensitive. Furthermore, suplatast tosilate significantly inhibited D_min. These results were especially significant in patients with atopic asthma. Suplatast tosilate was considered to have inhibited airway eosinophilic inflammation through decreases in peripheral blood eosinophils counts and in ECP levels in induced sputum, which resulted in inhibition of airway hyperresponsiveness.     

Effects of Suplatast Tosilate on Airway Inflammation and Airway Hyperresponsiveness

Suplatast tosilate (IPD®) is a Th2 cytokine inhibitor that lowers the titer of the IgE antibody through specific inhibition of the production of IL (interleukin)-4 and IL-5 by T cells and inhibits tissue infiltration by eosinophils. In this clinical trial, suplatast tosilate (300 mg/day) was administered orally for 4 weeks to 25 patients (13 patients with atopic asthma, 12 patients with nonatopic asthma) whose bronchial asthma was staged in step 1 or step 2 according to the Guidelines for Prevention and Management of Bronchial Asthma, 1998. Before and after administration, the parameters of airway inflammation, that is, peripheral blood eosinophils count, serum level of eosinophil cationic protein (ECP), ECP level in induced sputum, airway hyperresponsiveness (D_min), and morning peak expiratory flow (PEF), were measured. The peripheral blood eosinophil count, serum level of ECP, and ECP level in induced sputum decreased significantly. Of these parameters, the ECP level in induced sputum was the most sensitive. Furthermore, suplatast tosilate significantly inhibited D_min. These results were especially significant in patients with atopic asthma. Suplatast tosilate was considered to have inhibited airway eosinophilic inflammation through decreases in peripheral blood eosinophils counts and in ECP levels in induced sputum, which resulted in inhibition of airway hyperresponsiveness.     

Deposition of eosinophil cationic protein in vascular lesions in temporal arteritis.

The possible role of the eosinophil and its cytotoxic granule proteins in the vascular lesions seen in temporal arteritis was elucidated. Sixteen sections of biopsy specimens from arteria temporalis showing giant cell arteritis were stained for eosinophil cationic protein (ECP) by polyclonal antibodies and the immunoperoxidase method. Activated eosinophils were identified by monoclonal antibodies linked to alkaline phosphatase. Activated eosinophils and secreted ECP were seen in all layers of the inflamed vessels and were most evident in necrotic lesions and thrombi. Only a small number of granulocytes seen in the adventitia were immunoreactive for cathepsin G, and no extracellular deposits of this neutrophil granule protein were seen. A few immunoreactive eosinophils were found in the adventitia in two of five negative temporal artery biopsy specimens from patients with polymyalgia rheumatica. All eight coronary artery biopsy specimens with atherosclerotic lesions showed no activated eosinophils or secreted ECP. These findings indicate that eosinophils are involved in the vascular lesion in temporal arteritis and suggest that cytotoxic eosinophil granule proteins may contribute to the necrotic lesions and the development of thrombi.     

Role of aeroallergens in the etiopathogenesis of atopic dermatitis

Atopic dermatitis is a chronic relapsing inflammatory skin disease. It is most frequent in childhood and its clinical manifestations vary with age. The etiopathogenic mechanisms that explain this process are still poorly understood; several studies performed in adults speculate on the possible role of aeroallergens through direct contact with the skin but, because the etiology of this disease varies with age, studies in children of different ages are required.Aims: (i) To determine whether children with atopic dermatitis are sensitized to inhalant allergens. (ii) To determine whether these inhalant allergens cause dermatitis or whether they provoke allergic respiratory disease (asthma, rhinitis) concomitant with atopic dermatitis. (iii) To evaluate whether sensitization to a particular allergen takes place at any age or whether there are differences according to age.Material and methods: This study was performed in the following groups: (i) 64 children with atopic dermatitis, divided into two subgroups, one consisting of 37 children who also presented allergic respiratory disease (asthma, rhinitis) (AR) and another subgroup of 27 patients who presented atopic dermatitis only. (ii) Control group: eight children who presented AR only, to determine whether this group reacted to patch testing with inhalant allergens. (iii) Control group: seven healthy children to rule out non-specific positive tests in the non-atopic population. All groups were divided by age according to the phases of atopic dermatitis: early childhood phase (< 2 years): 21, childhood phase (2-10 years): 37, adolescent phase (> 10 years): 21. In all children total serum IgE determination (RIA), allergen-specific IgE determination (RAST), prick- and patch test were performed. In the three tests the same allergens were used, consisting of the usual components of standardized inhalant and food allergens. When the results of patch testing were positive, biopsy and histopathological analysis were performed and monoclonal antibodies were used to determine reproducibility of the eczematous lesion.Results: Sensitization was found to differ among patients with atopic dermatitis according to whether they presented respiratory symptoms and according to age with a clear predominance of food sensitization in the group aged less than 2 years. In the group aged 2-10 years, mixed sensitization predominated, mainly because of simultaneous respiratory involvement, but it is highly probably that inhalant allergens participate in the etiopathogenesis of atopic dermatitis. In children aged more than 10 years sensitization to inhalant allergens predominated as most presented respiratory symptoms. Patch testing was positive in 34.3 % of patients with atopic dermatitis and approximately half were positive to dust mites. The patch test is of great diagnostic value in atopic dermatitis and none of the tests were positive in the control group. All the biopsies of patch tests with inhalant allergens reproduced the lesions typical of eczema, demonstrating their involvement in the etiopathogenesis of dermatitis.     

Etiologic implication of foods in atopic dermatitis: evidence in favor

Some of the immunopathologic mechanisms involved in IgE responses are currently being identified; Th2 lymphocytes are known to be activated in patients with atopic dermatitis with subsequent production of the cytokines interleukin (IL)-4 and IL-5, which are responsible for IgE production and eosinophil recruitment. Nevertheless, T cell activation in this disease takes place in two phases. In the first phase, Th2 cells are activated and IL-4, IL-5 and IL-13 are produced; this first stage is produced with the initial activation induced by the antigen. In the second phase there are chronic lesions, Th1 lymphocytes are activated and IFg is produced. This chronic phase is associated with the presence of eosinophils and macrophages that produce IL-12.Numerous articles have demonstrated food sensitization to be an etiopathogenic factor in atopic dermatitis. The prevalence of sensitization varies, depending on the patient's age and the severity of the disease. Children with moderate-to-severe atopic dermatitis have been observed to have a positive skin test and high IgE concentrations to various foods. Nevertheless, a positive skin test to foods in such children does not always implicate these foods as the cause of the clinical manifestations; moreover, in children showing subsequent tolerance to these foods, skin tests can sometimes remain positive and high levels of specific IgE can persist. It is now known that IgE not only participate in the degranulation of mastocyte cells but also in reactions mediated by T cells and other antigen-presenting cells (dendritic cells) which have high-affinity receptors for IgE.The immediate IgE response is well known but it is also known that in addition to the immediate response, a delayed response is also involved, evidenced by the presence of antigen-specific T cells to foods or other allergens such as inhalant allergens. After a strict exclusion diet, children with atopic dermatitis and sensitivity to foods such as milk, egg, flour and soya can develop tolerance; for this reason provocation tests with the food in question should be repeated every 2-3 years. In children with sensitivity to other foods such as dried fruits, fish, and shellfish, sensitivity can sometimes persist into adulthood without tolerance being achieved. In conclusion, there are two groups of children with atopic dermatitis. One group consists of those with atopic dermatitis (allergic disease), which is characterized by early development, high IgE titers, the presence of antigen-specific IgE to allergens and a family history of atopy and which is clinically moderate or severe. Early diagnosis and treatment are important in these children, as is the prevention of progression of the disease to bronchial asthma. The other group consists of children whose dermatitis is clinically atopic in terms of its localization and morphology, who have no demonstrable allergic disease and whose management differs from that in children presenting allergic disease     

Eosinophil Activation in Ulcerative Colitis (Studies on Mucosal Release and Localization of Eosinophil Granule Constituents)

Activation of eosinophil granulocytes(eosinophils) seems to contribute to the pathophysiologyof several inflammatory conditions. This process wasevaluated in 18 patients with ulcerative colitis and in 18 healthy controls using intraluminalsegmental perfusion of the sigmoid colon and rectum andimmunoanalysis for eosinophil cationic protein (ECP) inthe perfusate. Immunohistochemistry for eosinophils and neutrophils was made in simultaneouslytaken biopsies and in biopsies from surgical specimenstaken from additional 10 patients. The mucosal releaseof ECP was increased severalfold in patients with UC. The bowel biopsies demonstrated a laminapropria infiltrated with eosinophils. The degree ofeosinophil activation/degranulation was related to theintensity of the inflammatory reaction. Activated eosinophils and extracellular deposits of ECPwere, in particular, seen in crypt abscesses and inareas with damaged surface epithelium. Since ECP ishighly cytotoxic, its release at the site ofinflammatory bowel lesions might reflect a potentialpathophysiological mechanism.     

Percutaneous sensitization to almond oil in infancy and study of ointments in 27 children with food allergy

A five month old child with atopic dermatitis developed contact dermatitis to almond with positive patch test, positive prick test, and class 4 anti-almond IgE. Focal lesions of persistent eczema were correlated with application of almond oil for 2 month on cheeks and buttocks. The child had not ingested almond and her mother did not report almond intake during her breast-feeding. This observation points to the problems of possible percutaneous sensitisation to food proteins. The study of skin ointments containing components of food origin in 27 food sensitized atopic patients confirm that the choice of an ointment for lesional skin is of importance.     

Modèle expérimental de dermatite atopique

Skin lesions in the allergic form of atopic dermatitis (AD) are induced by allergen-specific T cells which infiltrate the skin at the site of allergen exposure. The pathophysiology of atopic dermatitis is not entirely defined. Although Th2-type CD4⁺ T cells appear to be crucial in AD pathophysiology, little is known about the contribution of CD8⁺ T cells in the development of the allergic skin inflammation. In the present study, we have developed a mouse model of allergen-induced AD and we have analyzed the respective roles of CD8⁺ and CD4⁺ T cells in the development of AD skin lesions. In sensitized mice, CD8⁺ T cells are rapidly and transiently recruited to the allergen-exposed site and initiate the inflammatory process, leading to skin infiltration with eosinophils and Th1/Th2 producing cells. CD8⁺ T cell-depleted mice show no inflammation, demonstrating that these cells are mandatory for the development of AD. In contrast, CD4⁺ T cell-depleted mice develop a severe form of eczema. Furthermore, adoptive transfer of CD8⁺ T cells from sensitized mice into naive recipient mice leads to skin inflammation soon after allergen exposure. These data indicate that allergen-primed CD8⁺ T cells are required for the development of AD-like lesions in mice. Ongoing studies may allow us to confirm these findings in humans.     

The Role of the Histamine H4 Receptor in Atopic Dermatitis

The pathology of atopic dermatitis is orchestrated on the cellular level by several different cell types in the characteristic skin lesions. In such lesions, histamine as a mediator of many biological functions is also present in high concentrations. Most of the cells involved in the inflammatory responses express the histamine H1 and H2 receptors, but drugs targeting these receptors are not clinically effective. The discovery of the fourth histamine receptor, which is differentially expressed on immune and nonimmune cells, has shed new light on the actions of histamine in the complexity of atopic dermatitis. In this review, we describe a possible genetic impact on the expression level of the histamine H4 receptor and summarize the current data regarding the activity of the histamine H4 receptor on the key effector cells in atopic dermatitis. We do so in the context of whether the histamine H4 receptor offers a novel target for effective treatments of inflammatory skin diseases.