Pruritic Inflammatory Skin Disease Research Articles

Bacterial pattern and antibiotic sensitivity in children and adolescents with infected atopic dermatitis

Atopic dermatitis (AD) is a pruritic and chronic inflammatory skin disease which affected approximately 20% in children. Bacterial infection is common in AD patients and correlates directly with AD severity. A cross-sectional study was conducted to evaluate the prevalence of bacterial skin infection in AD patients and its relation with severity of AD and also to study bacteria in the infected AD and its antibiotic sensitivity. Samples were 86 children and adolescents with an AD in Helvetia Community Health Center Medan from March 2016 until February 2017. Index of SCORing Atopic Dermatitis (SCORAD) was used to evaluate the severity of AD. Lesion and nonlesional skinwere swabbed to take sterile cultures. All bacteria noted and tested for antibiotic sensitivity. Datawere by using Chi-Square and Mann Whitney test with 95% CI and p-value<0.05 was considered statistically significant. Fifty-six AD patients (65.1%) were bacterial infected. There was a significant relationship between severity of AD and bacterial infection (p = 0.006). Staphylococcus aureus was the leading bacteria from all degrees of AD severity. Isolated Staphylococcus aureuswas sensitive to amoxicillin-clavulanate (93.3%), clindamycin (90%), erythromycin (90%), and gentamicin (90%), while sensitivity to tetracycline was low (20%).

Dupilumab: an evidence-based review of its potential in the treatment of atopic dermatitis.

IntroductionAtopic dermatitis (AD) is a recurrent, pruritic inflammatory skin disease with complex immunopathogenesis characterized by a dominant TH2 response. Dupilumab is an interleukin (IL)-4 receptor alpha antagonist that subsequently blocks IL-4 and IL-13 signaling. It has recently been approved for the treatment of adult patients with moderate-to-severe AD whose current treatment options are limited.AimThis article reviews the evidence of clinical efficacy, safety, and patient-reported out-come (PRO) measures from Phase I–III trials of dupilumab in adult patients with moderate-to-severe AD.Evidence reviewResults from clinical trials of dupilumab in adults with moderate-to-severe AD have shown that weekly or biweekly dupilumab injections significantly improve clinical and PROs. Transcriptome and serum analyses also found that dupilumab significantly modulates the AD molecular signature and other TH2-associated biomarkers, compared with placebo. Additionally, concomitant use of dupilumab with topical corticosteroids (TCS) results in a greater improvement in signs and symptoms of AD than with dupilumab use alone. Throughout the trials, common adverse events were headaches, conjunctivitis, and injection site reactions. These were consistently mild–moderate and occurred with similar frequency between the treatment and placebo groups.Place in therapyIn adult patients with moderate-to-severe refractory AD, monotherapy or concomitant use of dupilumab with TCS holds great promise to significantly improve clinical outcomes and quality of life of the patient. Ongoing studies of dupilumab will help determine the clinical efficacy and safety profile of its long-term use. Finally, further economic evidence is warranted to compare the long-term costs and benefits of dupilumab with other currently available treatments for moderate-to-severe AD.

Increased risk of psoriasis following scabies infection: A nationwide population-based matched-cohort study.

Both scabies and psoriasis are pruritic inflammatory skin diseases. The clinical manifestations are similar and provocation of psoriasis by mite bite was reported. The association between scabies and psoriasis was not investigated before. We conducted this nationwide population-based matched-cohort study to describe if patients with a diagnosis of scabies have a different risk of developing new psoriasis. From the National Health Insurance Research Database of Taiwan, patients with scabies (n = 5137) were identified and matched for age and sex with non-scabies controls (n = 19 142). We tracked them for a 7-year period to identify the incidence of psoriasis. One hundred and ninety (0.8%) patients with newly diagnosed psoriasis were identified; 91 (1.8%) from the scabies group and 99 (0.5%) from the control group. Patients with scabies had a higher risk of subsequent psoriasis, with a crude hazard ratio of 3.45 and an adjusted hazard ratio (aHR) of 3.03 (95% confidence interval, 2.24-4.11). An increased risk for psoriasis among patients with scabies was observed (aHR, 3.03). Immunopathology involving the T-helper 17 cell-mediated inflammatory pathway may contribute to this association. Physicians may consider implementing assessments of psoriatic symptoms in patients with scabies.

Molecular Mechanism of Atopic Dermatitis Induction Following Sensitization and Challenge with 2,4-Dinitrochlorobenzene in Mouse Skin Tissue

Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T (TH1) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of TH1 cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

From Bench to Clinic: the Potential of Therapeutic Targeting of the IL-22 Signaling Pathway in Atopic Dermatitis.

Atopic dermatitis (AD) is the most common pruritic inflammatory skin disease characterized by thickening of epidermis and dermis as well as by the infiltration of multiple pathogenic polarized T lymphocytes, including Th2, Th17, and Th22 cells. Significant progress has been made to develop targeted therapeutics for treating AD, e.g., Food and Drug Administration-approved dupilumab, an antibody for dual targeting of IL-4 and IL-13 signaling pathways. Additionally, a growing body of published evidence and a promising result from the early stage of the clinical trial with ILV-094, an anti-IL-22 antibody, strongly support the notion that IL-22 is a potential therapeutic target for treating AD. Moreover, we also experimentally proved that IL-22 contributes to the pathophysiology of AD by employing a murine model of AD induced by epicutaneous sensitization. Here, we review recent preclinical and clinical findings that have advanced our understanding of the roles of IL-22 and Th22 cells in skin inflammation. We conclude that blockade of IL-22 signaling may be a promising therapeutic approach for the treatment of AD.

Biologic Therapy for Atopic Dermatitis: Moving Beyond the Practice Parameter and Guidelines

Atopic dermatitis (AD), a common chronic pruritic inflammatory skin disease, impacts the quality of life of patients and caregivers and has become a global health problem. It is increasingly recognized as a disease not only of children but also of adults who may have a persistent or relapsing course from childhood or who develop new-onset adult disease. Besides well-established atopic comorbidities, associations with a number of nonatopic comorbidities have been reported. AD is characterized by both immune dysregulation and epidermal barrier dysfunction. The findings that nonlesional skin in AD has both terminal keratinocyte differentiation defects and immune abnormalities as well as multiple markers of immune and inflammatory activation in the circulation point to the systemic nature of the disease and have important translational implications. Although AD is predominantly associated with type 2 immune responses, activation of other cytokine pathways including TH1, TH22, and TH17/IL-23 has been reported, suggesting potential therapeutic targets and provide a rationale for treatment with novel biologics. Dupilumab, a fully human mAb targeting the IL-4 Rα subunit, blocks signaling of both IL-4 and IL-13 and is the first biologic to be approved for the treatment of moderate-to-severe AD in adult patients. Other biologics in current trials for AD are targeting the IL-31 receptor, IL-13, and the common p40 subunit of IL-12/IL-23.

Anti-inflammatory effect of collagen tripeptide in atopic dermatitis

BackgroundAtopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease in which type 2 allergic inflammation plays an important role. Collagen tripeptide (CTP) is a functional collagen fraction with a high content of Gly-X-Y tripeptides. ObjectiveTo examine the effect of CTP on inflammation in AD. MethodsLevels of inflammatory cytokines and chemokines, such as thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine, and thymic stromal lymphopoietin (TSLP), were examined in human keratinocytes supplemented with or without CTP under AD-like inflammation. To evaluate the functional effect of CTP, a migration assay was performed using the supernatants of cultured keratinocytes treated with CTP. The signaling pathway for CTP inhibitory activity was also determined. Additionally, we conducted a clinical trial with seventeen AD patients who were assigned randomly to receive daily for 12 weeks either 3.9g of a CTP product or normal collagen peptides (CP). The eruption area, severity scoring of atopic dermatitis (SCORAD), skin hydration, transepidermal water loss (TEWL), and itching score were evaluated. The levels of TARC, serum IgE, lactate dehydrogenase, and eosinophil counts at week 12 were also compared with those at the start of administration. ResultsIn human keratinocytes, TARC and TSLP mRNA and protein levels were inhibited significantly by CTP treatment under AD-like inflammation. Supernatants obtained from CTP-treated keratinocytes inhibited cell migration. STAT1 phosphorylation was significantly decreased by CTP in a dose-dependent manner. In the clinical trial, 13 patients (7 for CTP, 6 for CP) completed the study. The eruption area, SCORAD, and TEWL at week 12 were reduced significantly compared with the initial values in the CTP but not CP group. A significant reduction in the serum TARC level was observed only in the CTP group at week 12. Other blood parameters were not improved in either group. ConclusionCTP may have therapeutic benefit for AD by inhibiting type 2-skewed allergic inflammation.

Topical application of Jaungo in atopic dermatitis patients: study protocol for a randomized, controlled trial

BackgroundAtopic dermatitis (AD) is a common pruritic inflammatory skin disease with increasing prevalence. It can manifest with many different clinical phenotypes; however, in its chronic stage, hyperpigmentation, excoriation, lichenification, and dryness are the main symptoms. Jaungo comprises two herbs, Lithospermi radix and Angelica gigantis radix, and three carrier oils, and is an approved herbal ointment for xerosis cutis in Korea. In past studies, we demonstrated that Jaungo had anti-inflammatory and antiallergic activity in in vitro and in vivo AD models; however, there are few relevant randomized controlled clinical trials on Jaungo in AD.Methods/designA randomized, double-blind, placebo-controlled, single-center, phase IIa clinical trial was designed to investigate the safety, preliminary efficacy, and dose response of Jaungo in AD. The study protocol was approved by the Institutional Review Boards of the Kyung Hee University Korean Medicine Hospital (No. KOMCIRB-160617-HR-027) and the Korea Food and Drug Administration (No. 30907). The study aims to enroll 34 AD patients to be randomly distributed among three parallel groups: treatment 1, treatment 2, and the placebo group. Treatment group 1 applies Jaungo twice a day, while treatment group 2 applies Jaungo and the placebo ointment once a day, separately, and the placebo group applies the placebo ointment twice a day, for a total of 3 weeks each. Participants will be evaluated for eczema before and after the application of the ointments based on several parameters including the Eczema Area and Severity Index, the SCORing of Atopic Dermatitis Index, the Dermatology Life Quality Index, transepidermal water loss, total IgE level, eosinophil count, and IL-17, IL-22, and IFN-γ levels.DiscussionThe trial is currently ongoing and the enrollment of subjects has been initiated. There is an urgent need to develop a drug for the treatment of dry, hyperpigmented, scaly, and thickened skin in chronic-stage AD. This study will determine the efficacy and safety of Jaungo in AD, providing evidence for specific AD symptoms treated by Jaungo.Trial registrationClinical Trials.gov, identifier: NCT02900131. Registered on 2 September 2016. Korea Clinical Research Information Service, identifier: KCT0002060. Registered on 22 July 2016.

Effect of DM extracts on the Atopy Dermatitis in human keratinocytes

Atopic dermatitis (AD), a pruritic chronical inflammatory skin disease is associated with a personal or family history of atopy such as asthma of respiratory diseases and or allergic rhinitis. The prevalence rate is increasing recently. This study was to evaluate the inhibitory effects performance by respectively of DM extracts (DME) from the tumor necrosis factor‐α (TNF‐α), interferon‐γ (IFN‐γ)‐induced inflammatory response in human keratinocytes. (HaCaT cells). HaCaT cells were each treated with 250 μg/mL respectively of DME water extract, 20% ethanol extract, and 50% ethanol extract. Also, investigated the effects of DME on the production of histamine in A23187 and PMA‐stimulated Mast cells. (MC/9 cells). We found that treatments with DME decreased the production of pro‐inflammatory cytokines in TNF‐α, IFN‐γ‐stimulated HaCaT cells, and the decrease in histamine release in the A23187 and PMA‐simulated Mast cells.

Selected comorbidities of atopic dermatitis: Atopy, neuropsychiatric, and musculoskeletal disorders

Atopic dermatitis (AD) is a chronic pruritic inflammatory skin disease with substantial morbidity and quality of life impairment. There are a number of comorbid health problems that occur in patients with AD, aside from the cutaneous signs and symptoms. Chronic pruritus and inflammation can lead to sleep disturbances and mental health symptoms, which are not mutually exclusive. AD is associated with and may predispose to higher risk of other atopic disorders, including asthma and hay fever. Persons with AD appear to be at higher risk for multiple neuropsychiatric disorders, including depression, attention-deficit/hyperactivity disorder, speech disorders in childhood, headaches, and seizures. There is also a multifactorial association of AD with osteoporosis, injuries, and fractures. Elucidating the comorbidities of AD is important for disease management and improving overall clinical outcomes. This review summarizes recent developments in the atopic and neuropsychiatric comorbidities of AD.

Knowledge, attitudes and practices of the medical personnel regarding atopic dermatitis in Yaound\xe9, Cameroon

BackgroundAtopic dermatitis (AD) is a chronic, relapsing and pruritic inflammatory skin disease whose management remains unclear to most non-dermatologists. This study aimed to assess the knowledge, attitudes and practices (KAP) of the medical staff regarding AD in Yaoundé, Cameroon.MethodsThis was a cross-sectional study conducted from January to April 2014 in 20 health facilities located in Yaoundé, the capital city of Cameroon. All medical staff who provided their consent were included in the study. A score was established for each of the KAP categories, and subsequently grouped into 4 classes considering a score <50, 50-<65, 65-<85 or ≥85%, respectively.ResultsWe enrolled 100 medical personnel, 62% of whom were females. Overall, the level of knowledge on AD was moderate (65%). Allergy was the main cause of AD, stated by 64% of participants. Only 43% personnel cited the genetic cause. Asthma was mentioned by 78% as an associated pathology. Regarding attitudes, the majority (84%) thought that AD is equally common among Black and Caucasian populations; 42% of participants believed that evolution is favorable when appropriate medical treatment is prescribed. These attitudes were considered wrong (64%). Similarly, the general level of practice was inadequate: 50%.ConclusionLevels of knowledge, attitudes and practices of the medical staff regarding AD were poor, implying that management of this condition is non optimal in our setting.

Evaluation of serum periostin level in atopic dermatitis patients

Background Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease. Periostin is an intrinsic mediator induced by T helper-2 cytokines. It has been reported to play a critical role in the pathogenesis of AD. Objective The objective of this study was to estimate the serum periostin level in AD patients and to determine its correlation with the severity and chronicity of the disease. Patients and methods This study included 36 AD patients and 36 healthy controls, matched for age and sex. Three millimeters of venous blood was collected from each patient. Serum periostin level was determined by enzyme-linked immunosorbent assay. We determined the correlation between serum periostin level, duration of disease, severity, type of atopy, and SCORAD score. Results There were highly significant differences between patients and controls as regards serum periostin level (P Conclusion Serum periostin level may correlate with disease severity and chronicity in patients with AD.

Impact of UVA on pruritus during UVA/B phototherapy of inflammatory skin diseases: a randomized double-blind study.

Narrowband (TL-01) UVB phototherapy (UVB nb) is effective in treating inflammatory skin disease. The addition of UVA is traditionally advocated to reduce pruritus, but lacks evidence for this recommendation. The aim of this study was to assess the effect of UVB nb and UVA phototherapy in combination compared against UVB nb monotherapy on pruritus, disease activity and quality of life. In this double-blind randomized clinical trial, 53 patients suffering from inflammatory skin diseases with pronounced itching (Visual Analogue Scale (VAS) for pruritus ≥5) were randomized into two treatment groups. One group received UVB nb (311 nm) phototherapy alone and another group received a combination of UVB nb and UVA (320-400 nm) phototherapy. UV therapy was performed three times per week over 16 weeks. Pruritus (VAS and 5-D itch score), disease activity and quality of life (Dermatology Life Quality Index, DLQI) were assessed at baseline and weeks 4, 8, 12 and 16. In both treatment groups, there was a reduction in pruritus scores, disease activity and DLQI. No difference in pruritus score, disease activity and quality of life could be detected between the group receiving UVB nb alone and those receiving UVB nb combined with UVA. Phototherapy with UVB nb alone, and UVB nb combined with UVA are equally effective in treating inflammatory skin disease and indifferent in reducing disease-associated pruritus. Given this non-inferiority for UVB nb monotherapy, the recommendation of adding UVA to UVB nb phototherapy for pruritic inflammatory skin disease should be abandoned.

Review of Systemic Treatment Options for Adult Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease resulting from defects in skin barrier and aberrant immune responses. AD significantly affects the quality of life. Not all patients respond to topical therapies, and often systemic therapy is required to control the disease. To review the treatment options for adult AD patients including those options for patients who do not respond adequately or have contraindications to oral systemic therapy. A working group of clinicians with experience managing AD was convened to review the current literature on treatment options for adult AD patients. This review is based on the best available evidence from a published systematic review and an additional literature search. Current treatments for AD are reviewed, including options for adult AD patients who do not respond or have contraindications to current systemic therapies. A new approach with targeted therapies is reviewed based on best available evidence. Many AD patients respond satisfactorily to topical or systemic treatments, but for those patients who do not respond or have contraindications, new biologic agents appear to be promising therapies.

Potential Treatments for Atopic Dermatitis

Atopic Dermatitis (AD) is the most common pruritic inflammatory skin disease which causes economic and social burden. AD is not curable and therapeutic options are limited. Currently, the therapeutic approaches to AD include topical treatment, phototherapy, and systemic treatment. Although traditional therapeutic strategies are efficacious in ameliorating the symptoms of AD in most patients, sometimes it is a tough challenge for physicians as AD is catastrophic and difficult to treat. Several potential treatments for AD are being studied owing to a clearer understanding of its pathogenesis. Additionally, animal models of AD allow comprehensive and thorough investigation of pathogenesis and provide more options of therapeutic interventions. The purpose of non-classical treatment strategies for AD is to decrease skin inflammation, re-direct the imbalanced immune polarization, and induce immune tolerance to allergens. Generally, the intervention for mouse model of AD can be classified into 1) monoclonal antibodies, 2) anti-oxidants, 3) allergen-specific immunotherapy, 4) herbal medicine, 5) treatment with materials extracted from food or micronutrients, 6) microbiota/probiotics, 7) bio-composites films, and 8) others. Since half of the patients with AD lack specific immunoglobulin E against allergens, the pathogenesis of different phenotypes still needs to be clarified. Through novel therapies such as cytokine-targeting therapy, miRNA or suppression of thymic stromal lymphopoietin, patients with AD could have better quality of life with less morbidity.

Histopathological diagnosis of atopic eruption of pregnancy and polymorphic eruption of pregnancy: a study on 41 cases.

The specific dermatoses of pregnancy represent a recently reclassified heterogeneous group of pruritic inflammatory skin diseases unique to pregnancy that include pemphigoid gestationis, polymorphic eruption of pregnancy (PEP), intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy (AEP). Among them, PEP and AEP are the most frequent ones. We performed a histopathological study of a series of PEP and AEP patients (n = 41). Twenty-two patients had PEP that started in the third trimester in 16 (73%) patients and postpartum in 6 (27%) patients. Histopathology revealed a superficial or superficial and deep perivascular dermatitis with eosinophils in all biopsies and signs of a lymphocytic vasculitis in 5 (23%) cases. Epidermal changes, including epidermal hyperplasia, spongiosis, and parakeratosis, occurred in 8 cases, in particular in elder lesions. Nineteen patients had AEP that started earlier [less than third trimester, 14 (74%) patients; third trimester, 5 (26%) patients]. Clinically, 5 (26%) patients showed eczematous lesions, 7 (37%) papular lesions, 3 (16%) presented both eczematous and prurigo lesions, and 4 (21%) experienced exacerbation of preexisting atopic dermatitis. Histopathologically, AEP was characterized by a perivascular lymphohistiocytic infiltrate with frequent eosinophils (74%) and epidermal changes in all but most of P-type biopsies. No definitive differential histopathological criteria between PEP and AEP were found. Only lymphocytic vasculitis with a mixed infiltrate with eosinophils was more frequent in PEP patients. Timing of onset, morphology of skin lesions, and a detailed clinicopathologic correlation are essential for diagnosis.

A mouse model of atopic dermatitis.

Atopic dermatitis (AD) is a chronic or chronically relapsing, pruritic inflammatory skin disease. The incidence of AD has dramatically increased for the past three decades in industrialized countries. We established a highly efficient method to induce AD-like skin lesions using repeated epicutaneous treatments with house dust mite allergen and staphylococcal enterotoxin B (SEB). The dermatitis-induced mice showed increased serum IgE levels that were similar to human AD patients and also treatable with dexamethasone. This mouse AD model has been used in a vaccinia virus infection study. It will also be useful to study pathogenic processes of AD and to evaluate the efficacy of a drug candidate. In this chapter, we describe the detailed method that can induce AD-like skin inflammation in multiple mouse strains.

Atopic Dermatitis: Insights on Pathogenesis, Evaluation and Management

Background: Atopic Dermatitis (AD) is a highly pruritic chronic inflammatory skin disease that commonly presents during early childhood. Several studies indicate that the disease is very common in western world with lifetime prevalence in children of 10% to 20%. Data sources: We make recommendations regarding the evaluation and management of AD in children based on systematic literature searches using the best-available evidence from PubMed, Medline, Google Scholar, NICE, the American Academy of Dermatology and the World Allergy Organization. Results: AD has an immunologic basis. Both innate and adaptive immune responses are impaired in AD patients. Intense pruritus is a hallmark of the disease which leads to extensive scratching and further breakdown of the skin barrier. Treatment of AD may be topical or systemic. Topical corticosteroids and calcineurin inhibitors are used as topical anti-inflammatory agents. Patients should be carefully instructed in the use of topical glucocorticoids to avoid side effects. Conclusions: Treatment of atopic eczema should be based on a “stepped-care plan” where treatments are stepped up or down depending on the assessment of the state of the child’s skin by the physician. Physicians who treat children with mild to moderate AD should tell children and their caregivers that AD is a lifelong illness.

Mast Cells Are Required for Full Expression of Allergen/SEB-Induced Skin Inflammation

Atopic dermatitis is a chronic pruritic inflammatory skin disease. We recently described an animal model in which repeated epicutaneous applications of a house dust mite extract and staphylococcal enterotoxin B induced eczematous skin lesions. In this study we showed that global gene expression patterns are very similar between human atopic dermatitis skin and allergen/staphylococcal enterotoxin B-induced mouse skin lesions, particularly in expression of genes related to epidermal growth/differentiation, skin-barrier, lipid/energy metabolism, immune response, or extracellular matrix. In this model, mast cells and T cells, but not B cells or eosinophils, were shown to be required for the full expression of dermatitis, as revealed by reduced skin inflammation and reduced serum IgE levels in mice lacking mast cells or T cells (TCRβ−/− or Rag1−/−). The clinical severity of dermatitis correlated with the numbers of mast cells, but not eosinophils. Consistent with the idea that Th2 cells play a predominant role in allergic diseases, the receptor for the Th2-promoting cytokine thymic stromal lymphopoietin and the high-affinity IgE receptor, FcεRI, were required to attain maximal clinical scores. Therefore, this clinically relevant model provides mechanistic insights into the pathogenic mechanism of human atopic dermatitis.

Anti-Inflammatory Effect of Quercetagetin, an Active Component of Immature Citrus unshiu, in HaCaT Human Keratinocytes

Citrus fruit contain various flavonoids that have multiple biological activities. However, the content of these flavonoids are changed during maturation and immature Citrus is known to contain larger amounts than mature. Chemokines are significant mediators for cell migration, while thymus and activation-regulated chemokine (TARC/CCL17) and macrophage-derived chemokine (MDC/CCL22) are well known as the typical inflammatory chemokines in atopic dermatitis (AD), a pruritic and chronic inflammatory skin disease. We reported recently that the EtOH extract of immature Citrus unshiu inhibits TARC and MDC production. Therefore, we investigated the activity of flavonoids contained in immature Citrus on TARC and MDC levels. As a result, among the various flavonoids, quercetagetin has stronger inhibitory effects on the protein and mRNA expression of TARC and MDC than other flavonoids. Quercetagetin particularly has better activity on TARC and MDC level than quercetin. In HPLC analysis, the standard peak of quercetagetin matches the peaks of extract of immature C. unshiu. This suggests that quercetagetin is an anti-inflammatory component in immature C. unshiu.