Administration of poly(I:C) improved dermatophagoides farinae-induced atopic dermatitis-like skin lesions in NC/Nga mice by the regulation of Th1/Th2 balance

Atopic dermatitis (AD) is characterized by a chronic and replapsing skin disease with Th2-dominant allergic inflammation. Poly(I:C) has been shown to have immunopotentiator properties, but its effect on AD has not been examined. In this study, the immunomodulatory effects of poly(I:C), using dermatophagoides farinae (Df)-induced AD-like skin lesions in NC/Nga mice, were investigated. The clinical scores were reduced significantly by the treatment with poly(I:C) at 25 and 50 μg/mouse. Histological analysis of the skin also revealed that treatment of poly(I:C) at 25 and 50 μg/mouse significantly reduced the inflammatory cellular infiltrate, including mast cells and eosinophils. Moreover, poly(I:C) increased the level of IFN-γ, a Th1 cytokine, whereas decreasing that of selective Th2 cytokine both in vivo and in vitro. The levels of serum IgE and Th2 chemokines such as eotaxin, TARC, in spleen cells were also reduced by poly(I:C). These results suggest that poly(I:C) inhibit the development of Df-induced AD-like skin lesions in NC/Nga mice through regulation of the Th1/Th2 balance. Therefore, our results indicate that poly(I:C) might be a useful immunomodulatory agent for the treatment of human AD.     

Genistein suppresses development of spontaneous atopic-like dermatitis in NC/Nga mice

In this study, we examined the effect of genistein on the severity of dermatitis and level of serum IgE in NC/Nga (NC) mice. NC mice housed in conventional conditions develop spontaneous atopic-like dermatitis; however, oral administration of 20 mg/kg genistein suppresses the development of dermatitis. We also investigated the levels of serum IgE in genistein-treated NC mice and found that the levels were the same as those in control NC mice. We further investigated in vitro IFN-gamma and IL-4 production from spleen cells upon stimulation with anti-CD3 and anti-CD28 mAbs. IFN-gamma production level in NC mice that received 20 mg/kg genistein was significantly lower than that in control NC mice. In contrast, the production level of IL-4 in genistein-treated mice was not significantly different from that in control mice but tended to increase in a dose-dependent manner.     

吴茱萸次碱对硝基氯苯诱导的Nc／Nga小鼠特应性皮炎样皮损的影响

目的观察吴茱萸次碱对特应性皮炎动物模型Nc／Nga小鼠的作用。方法外用2,4-二硝基氯苯（DNcB）反复刺激Nc／Nga小鼠建立特应性皮炎动物模型,通过观察皮肤组织病理学切片、免疫学指标评价皮炎损伤程度,观察吴茱萸次碱对特应性皮炎动物模型Nc／Nga小鼠的治疗作用。结果外用DNCB可以引起Nc／Nga小鼠湿疹样皮炎的产生;模型组小鼠血浆IgE水平（124．42±11．14ng／m1）较正常对照组（17．22±3．56ng／m1）增高（P〈0．05）;治疗组IL-12和IFN-γ水平（62．12±3．14pg／ml,68．29±1．39pg／m1）较模型组血浆IL-12和IFN-γ水平（20．14±6．15pg／ml,51．23±1．45pg／m1）增高,IgE水平（69．17±4．15ng／m1）较模型组IgE水平下降（P〈0．05）;醋酸地塞米松组血浆IL-12、IFN-γ和IgE水平（59．15±1．24pg／ml,64．12±1．19pg／ml,6817±1．15ng／ml）与治疗组比较,差异无统计学意义（P〉0．05）。结论吴茱萸次碱可能通过促进IL-12和IFN-γ分泌,抑制IgE的合成,发挥治疗NdNga小鼠特应性皮炎样皮损的作用。     

Low-dose ethanol aggravates allergic dermatitis in mice

Alcohol injures dendritic cells and suppresses cellular immunity, while some evidence indicates that drinking alcohol aggravates allergic asthma. This study investigated the effect of low doses of ethanol in enhancing allergic reactions in the skin of mice. Liquid food containing alcohol was administered to conventional NC/Nga mice to induce alcoholic hepatic steatosis, and spontaneous dermatitis was evaluated. BALB/c mice were administered approximately 1 g/kg body weight of ethanol by gavage, and contact hypersensitivity (CHS) or active cutaneous anaphylaxis (ACA) was induced. Spleens were collected 24 h after the elicitation of CHS and mRNA expressions of interferon (IFN)-γ, interleukin (IL)-4, IL-6, IL-10, and IL-18 were measured by quantitative RT-PCR. Alcohol-containing diet exaggerated spontaneous dermatitis in conventional NC/Nga mice and contact hypersensitivity in BALB/c mice. Ethanol administered by gavage for 5 days enhanced contact hypersensitivity in BALB/c mice. Ethanol administration with gavage also enhanced ACA of BALB/c mice. Ethanol did not affect mRNA expression of IFN-γ and IL-4, but did enhance IL-6, IL-10, and IL-18 mRNA expression. Histological evaluation revealed an absence of hepatic steatosis in mice administered ethanol by gavage for 5 days. In ethanol-administered mice, inflamed areas presented as lesions or a local extreme accumulation of mononuclear cells in the epidermis. These findings suggest that ethanol enhances the expression of inflammatory cytokines independently from T helper (Th)1/Th2 cytokine phenotypes, causing abnormalities in the epidermis resulting in exacerbated allergic reactivity.     

Enhancement of IFN-gamma production for Th1-cell therapy using negatively charged liposomes containing phosphatidylserine

We have developed an efficient method of interferon-gamma (IFN-gamma) induction for Th1-cell therapy. OVA (ovalbumin)-specific Th1 clone 42-6A cells cocultured with antigen presenting cells (APCs) from spleen resulted in high levels of OVA-specific IFN-gamma production by the treatment of phosphatidylserine (PS), but not phosphatidic acid (PA), liposomes-encapsulated OVA (OVA-liposomes). The IFN-gamma production was increased in a manner dependent on the PS content of the liposomes and inhibited by the addition of annexin V, a PS binding protein. Furthermore, coadministration of Th1 cells plus OVA-liposomes in mice strikingly enhanced IFN-gamma levels in serum and in spleen cells compared with that of Th1 cells plus OVA. In addition, serum levels of IL-12 p70 increased and ongoing OVA-specific IgE immune response was dramatically attenuated. These results first suggest that antigen delivery using negatively charged liposomes containing PS is very useful for the enhancement of IFN-gamma production in Th1-cell therapy.     

2,4-Dinitrofluorobenzene-induced contact hypersensitivity response in NC/Nga mice fed fructo-oligosaccharide

Strategies to manipulate gut microbiota in infancy have been considered to prevent the development of allergic diseases later in life. We previously demonstrated that maternal dietary supplementation with fructo-oligosaccharide (FOS) during pregnancy and lactation modulated the composition of gut microbiota and diminished the severity of spontaneously developing atopic dermatitis-like skin lesions in the offspring of NC/Nga mice. The present study tested whether dietary FOS affects contact hypersensitivity (CHS), another model for allergic skin disease, in NC/Nga mice. In experiment 1, 5-wk-old female NC/Nga mice were fed diets either with or without FOS supplementation for 3 wk and then received 2,4-dinitrofluorobenzene (DNFB) on the ear auricle 5 times at 7-d intervals. FOS supplementation reduced CHS response as demonstrated by ear swelling. Quantitative RT-PCR analysis showed that mRNA levels for interleukin (IL)-10, IL-12p40, and IL-17 in the lesional ear skin were significantly lower in mice fed FOS. In experiment 2, female NC/Nga mice were fed diets either with or without FOS during pregnancy and lactation. After weaning, offspring were fed the diets supplemented with or without FOS. Three weeks after weaning, offspring received DNFB on the ear auricle 4 times at 7-d intervals. Although FOS supplementation after weaning reduced ear swelling, maternal FOS consumption was ineffective in offspring. The present data suggest that dietary FOS reduces CHS while maternal FOS consumption is ineffective in offspring of DNFB-treated NC/Nga mice.     

Protease-resistant fraction of smoked, dried bonito alleviates atopic dermatitis-like skin lesions in NC/Nga mice

The effect of smoke-dried bonito undigested fraction remaining after microbial protease treatment (SDBR) on a spontaneously occurring mouse model of atopic dermatitis was studied in male 5-wk-old, NC/Nga mice. Smoke-dried bonito, Katsuobushi, is a traditional Japanese food. SDBR contains 2 major components: bonito oil and protease-undigested proteins. Mice were fed a casein diet containing corn oil (C diet) or a diet containing SDBR (SDBR diet) for 18 wk. In comparison with the C diet, the SDBR diet alleviated the increase in skin severity score and plasma IgE concentration in a time-dependent manner, and lowered leucotriene B(4) (LTB(4))-releasing ability upon calcium ionophore A23187 stimulation. The SDBR diet did not affect scratching time. These results demonstrate that SDBR diet alleviates atopic dermatitis-like skin lesions in NC/Nga mice.     

Lithospermum erythrorhizon Alleviates Atopic Dermatitis-like Skin Lesions by Restoring Immune Balance and Skin Barrier Function in 2.4-Dinitrochlorobenzene-Induced NC/Nga Mice

The incidence of atopic dermatitis (AD), a disease characterized by an abnormal immune balance and skin barrier function, has increased rapidly in developed countries. This study investigated the anti-atopic effect of Lithospermum erythrorhizon (LE) using NC/Nga mice induced by 2,4-dinitrochlorobenzene. LE reduced AD clinical symptoms, including inflammatory cell infiltration, epidermal thickness, ear thickness, and scratching behavior, in the mice. Additionally, LE reduced serum IgE and histamine levels, and restored the T helper (Th) 1/Th2 immune balance through regulation of the IgG1/IgG2a ratio. LE also reduced the levels of AD-related cytokines and chemokines, including interleukin (IL)-1β, IL-4, IL-6, tumor necrosis factor-α (TNF-α), thymic stromal lymphopoietin, thymus and activation-regulated chemokine, macrophage-derived chemokine, regulated on activation, normal T cell expressed and secreted, and monocyte chemoattractant protein-1 in the serum. Moreover, LE modulated AD-related cytokines and chemokines expressed and secreted by Th1, Th2, Th17, and Th22 cells in the dorsal skin and splenocytes. Furthermore, LE restored skin barrier function by increasing pro-filaggrin gene expression and levels of skin barrier-related proteins filaggrin, involucrin, loricrin, occludin, and zonula occludens-1. These results suggest that LE is a potential therapeutic agent that can alleviate AD by modulating Th1/Th2 immune balance and restoring skin barrier function.     

Anti-Inflammatory and Immune Modulatory Effects of Synbio-Glucan in an Atopic Dermatitis Mouse Model

Many trials have been conducted to treat atopic dermatitis (AD), but these therapies are generally unsuccessful because of their insufficiency or side effects. This study examined the efficacy of β-glucan derived from oats with fermented probiotics (called Synbio-glucan) on an AD-induced mouse model. For the experiment, Nc/Nga mice were exposed to a house dust mite extract (HDM) to induce AD. The mice were placed in one of four groups: positive control group, Synbio-glucan topical treatment group, Synbio-glucan dietary treatment group, and Synbio-glucan topical + dietary treatment group. The experiment revealed no significant difference in the serum IgE concentration among the groups. Serum cytokine antibody arrays showed that genes related to the immune response were enriched. A significant difference in the skin lesion scores was observed between the groups. Compared to the control group tissue, skin lesions were alleviated in the Synbio-glucan topical treatment group and Synbio-glucan dietary treatment group. Interestingly, almost normal structures were observed within the skin lesions in the Synbio-glucan topical + dietary treatment group. Overall, the β-glucan extracted from oats and fermented probiotic mixture is effective in treating atopic dermatitis.     

Vitamin E Improves Biochemical Indices Associated with Symptoms of Atopic Dermatitis-Like Inflammation in NC/Nga Mice

We aimed to define whether vitamin E improves biochemical indices associated with symptoms of atopic dermatitis-like inflammation in NC/Nga mice. After picryl chloride (PC) application to their backs, changes in the content of thiobarbituric acid reactive substances (TBARS) and vitamin E, as well as the activity of antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase) were analyzed in the serum and skin of NC/Nga mice during a symptomatic cycle. The levels of inflammatory factors were also assessed, including IgE, cyclooxigenase-2 (COX-2), tumor necrosis factor (TNF-α) and nuclear factor-κB (NF-κB). When allergic dermatitis was induced by the application of PC to the skin of the mice, skin inflammation appeared 2 wk after PC application, with the peak severity of inflammation observed 5 wk after PC application. Subsequently, the animals recovered from the inflammation by 9 wk after PC application. The TBARS content in the skin and serum increased markedly when the symptoms were the most severe, and decreased to levels near those in control mice by 9 wk after PC application. The activities of SOD and GSHPx in the skin and serum were also positively correlated with symptomatic changes; however, no change in catalase activity was observed 5 wk after PC application. Conversely, vitamin E content decreased at the stage of peak severity. The levels of all inflammatory factors analyzed in this study were altered in a manner similar to other indices. Additionally, vitamin E treatment markedly inhibited these PC-induced alterations. On the basis of these results, it is expected that the observed alterations in biochemical indices, which reflect the symptomatic cycle, may be applicable to objective diagnosis and treatment for atopic dermatitis, and that vitamin E may improve the symptoms of AD.     

Dietary ribonucleotides modulate type 1 and type 2 T-helper cell responses against ovalbumin in young BALB/cJ mice

Dietary ribonucleotides have been shown to augment type 1 T-helper cell (Th1) responses to a protein antigen (Ag) in Th1-prone C57BL/6 mice, but their effects on type 2 Th (Th2)-prone mice are unknown. BALB/cJ mice have skewed Th2 responses against ovalbumin (OVA), characterized by augmented production of Th2 cytokines and immunoglobulin (Ig)G1/IgE antibodies (Ab); Th1 responses augment IgG2a Ab production, whereas Th2 responses augment IgG1/IgE Ab production. In this study, we determined the effects of dietary ribonucleotides obtained from yeast on the balance of Th1/Th2 responses against OVA in young BALB/cJ mice. Mice were fed a ribonucleotide-free (NF) or ribonucleotide-supplemented (NS) diet (4.74 g nucleotides/kg diet) and given OVA (10 microg/dose) with incomplete Freund's adjuvant (IFA) at 3 and 6 wk. We assessed T-cell responses in the regional draining lymph nodes (LN) by measuring production and expression of Th1/Th2 cytokines, interferon-gamma (IFN-gamma) and interleukin-5 (IL-5), respectively. Anti-OVA IgG subclass and IgE Ab levels were determined 3 wk after the first OVA challenge and 5 d and 2 wk after the second OVA challenge. Dietary ribonucleotides significantly augmented OVA-specific IFN-gamma production by the regional draining LN cells after the first and second OVA challenges. The NS diet increased anti-OVA IgG2a Ab levels after the first OVA challenge and both anti-OVA IgG2a and anti-OVA IgG2b after the second challenge. OVA-specific IgG1 and IgE Ab levels were lower (P < 0.05) after the second OVA challenge in mice fed the NS diet. Dietary ribonucleotides did not affect production or expression of IL-5. Our findings thus indicate that in Th2-prone BALB/c J mice, dietary ribonucleotides modulated skewed Th2 responses against OVA toward Th1 as measured by production of IFN-gamma, a Th1 cytokine, and changes in anti-OVA Ab isotype levels.     

Siraitia grosvenorii Residual Extract Attenuates Atopic Dermatitis by Regulating Immune Dysfunction and Skin Barrier Abnormality

Atopic dermatitis is a persistent inflammatory skin disorder. Siraitia grosvenorii fruits (monk fruit or nahangwa in Korean, NHG) are used as a natural sweetener and as a traditional medicine for the treatment of asthma and bronchitis. We evaluated the activity of S. grosvenorii residual extract (NHGR) on allergic inflammation of atopic dermatitis in a Dermatophagoides farinae mite antigen extract (DfE)-treated NC/Nga murine model and in vitro. Oral administration of NHGR significantly reduced epidermal hyperplasia and inflammatory cell infiltration in the skin lesions of DfE-induced atopic dermatitis, as well as the dermatitis severity score. NHGR reduced serum immunoglobulin E levels. Splenic concentrations of IFN-γ, interleukin (IL)-4, IL-5, and IL-13 were reduced by NHGR administration. Immunohistofluorescence staining showed that NHGR administration increased the protein levels of claudin-1, SIRT1, and filaggrin in atopic dermatitis skin lesions. In addition, NHGR inhibited the phosphorylation of mitogen-activated protein kinases and decreased filaggrin and chemokine protein expression in TNF-α/IFN-γ-induced human keratinocytes. Moreover, NHGR also inhibited histamine in mast cells. The quantitative analysis of NHGR revealed the presence of grosvenorine, kaempferitrin, and mogrosides. These results demonstrate that NHGR may be an efficient therapeutic agent for the treatment of atopic dermatitis.     

Further evidence regarding the effect of dietary protein on oral tolerance against beta-lactoglobulin through Th1-mediated immune response in mice

Oral tolerance is a potential strategy for preventing or minimizing aberrant immune responses. Although, oral tolerance has been extensively studied, to date the effects of dietary protein on the induction of oral tolerance are poorly understood. We have previously shown that restricted dietary protein induces oral tolerance to ovalbumin. This study was designed to investigate whether or not such tolerance occurs with beta-lactoglobulin (BLG) instead of ovalbumin (OVA) and if the tolerance resulting from this feeding regimen involves Th1-mediated immune response. Female BALB/c mice fed either 20% or 5% dietary protein were given 5 mg BLG or water orally for four consecutive days and then immunized intraperitoneally (ip) twice with BLG at 3-wk intervals. Oral tolerance induction was compared in BLG-fed and water-fed mice by measuring total IgE, BLG-specific antibodies, footpad reactions, splenocyte proliferation, and cytokine production. When mice were given BLG orally before ip immunization, the Th1-mediated immune responses (production of IL-2, IFN-gamma, and IgG2a) were significantly reduced, whereas the Th2-mediated immune responses (production of IL-4 and IgG1) were unchanged. The Th1-mediated immune responses were markedly down-regulated in mice fed 5% protein as compared to those in mice fed 20% protein. Moreover, the production of total IgE, BLG-specific IgE, splenocyte proliferation, and footpad reactions were more reduced in mice fed 5% protein than those in mice fed 20% protein. The present study provides evidence that dietary protein plays an important role in the induction of oral tolerance against BLG as the result of, clear down-regulation of Th1 helper activity accompanied by a reduction in IgE.     

Cytokine mRNAs in the nasal-associated lymphoid tissue during influenza virus infection and nasal vaccination

Intranasal immunization with a current inactivated influenza vaccine together with an adjuvant (cholera toxin B subunit supplemented with a trace amount of whole toxin, CTB*) was confirmed in BALB/c mice to mimic influenza virus (A/PR/8/34, H1N1) infection with respect to mucosal IgA antibody responses, in which IgA antibody-forming cell responses in the nasal-associated lymphoid tissue (NALT) were involved with a peak around 7 days after infection or vaccination. Next, the expression of various cytokine mRNAs in the NALT was compared in mice either infected with viruses or immunized with CTB*-combined vaccine, to examine Th cell and cytokine regulation of mucosal IgA antibody responses. In infected mice, strong IL-2, weak IL-4, strong IL-6 and strong IFN-gamma mRNA expressions were induced during early days of infection; especially, IFN-gamma mRNA was expressed by both CD4(+) and CD8(+) T cells around 7 days after infection. In mice given CTB*-combined vaccine, weak IL-2, strong IL-4, strong IL-6 and weak IFN-gamma mRNA expressions were induced during early days of vaccination; especially, IL-4 mRNA was expressed by CD4(+) T cells. Thus, IL-6 mRNAs were expressed strongly in both infected and vaccinated mice. The IFN-gamma-rich cytokine mRNA profiles in the infected mice were reflected upon serum IgG2a-rich Ab responses, while the IL-4-rich profiles in the vaccinated mice were reflected upon the IgG1-rich Ab responses. Thus, influenza virus infection and CTB*-combined nasal vaccine induced Th1 dominant and Th2 dominant cytokine profiles, respectively, while the similarity of mucosal IgA antibody responses between infection and vaccination could be explained by the appearance of IL-6 mRNAs.     

Influence of the route of administration on immunomodulatory properties of bovine β-lactoglobulin-producing Lactobacillus casei

Because of their intrinsic immunomodulatory properties, some lactic acid bacteria were reported to modulate allergic immune responses in mice and humans. We recently developed recombinant strains of Lactobacillus casei that produce β-lactoglobulin (BLG), a major cow's milk allergen. Here, we investigated immunomodulatory potency of intranasal and oral administrations of recombinant lactobacilli on a subsequent sensitization of mice to BLG. Intranasal administration of the BLG-producing Lb. casei stimulated serum BLG-specific IgG2a and IgG1 responses, and fecal IgA response as well, but did not inhibit BLG-specific IgE production. In contrast, oral administration led to a significant inhibition of BLG-specific IgE production while IgG1 and IgG2a responses were not stimulated. After both oral and intranasal administrations, production of IL-17 cytokine by BLG-reactivated splenocytes was similarly enhanced, thus confirming the adjuvant effect of the Lb. casei strain. However, a mixed Th1/Th2 cell response was evidenced in BLG-reactivated splenocytes from mice intranasally pretreated, with enhanced secretions of Th1 cytokines (IFN-γ and IL-12) and Th2 cytokines (IL-4 and IL-5) whereas only production of Th1 cytokines, but not Th2 cytokines, was enhanced in BLG-reactivated splenocytes from mice orally pretreated. Our results show that the mode of administration of live bacteria may be critical for their immunomodulatory effects.     

Comparison of phage pVIII and KLH as vector in inducing the production of cytokines in C57BL/6J mice

We have demonstrated that phage display Candida albicans (C. albicans) LKVIRK epitope was protective in systemically infected C57BL/6J mice. The different development from precursor Ths, Th1 or Th2, will result in a protective or nonprotective immune response. To compare the types of cytokines induced by biologically and chemically synthesized vectors, C57BL/6J mice were immunized with hybrid phage displaying the epitope of LKVIRK and by synthesized peptide epitope LKVIRKNIVKKMIE conjugated through cysteine to keyhole limpet haemocyanin (KLH). The production of cytokines in spleens of immunized mice and in splenocytes culture supernatants stimulated by homologous immunogen in vitro was studied by RT-PCR and quantitative sandwich ELISA. The results showed that, compared to Tris-EDTA buffer (TE, 1 mM Tris, 0.1 mM EDTA, pH 8.0) injected mice, the expressions of Th1 type cytokine IFN-gamma, IL-2 and IL-12 were increased in hybrid phage, KLH-C, and wild phage immunized mice, and there were no differences between mice immunized with hybrid phage and KLH-C. While the expression of Th2 type cytokine IL-10 was similar in all mice, IL-4 was not detected. We obtained the same results in mRNA and protein level. These findings indicated that as carriers, phage and KLH were similar in inducing the Th1 type cytokines expression. Comparing to peptide synthesis couple with a carrier protein for injection, phage may be an inexpensive and simple route to the production of effective vaccines.     

Di-(2-ethylhexyl) phthalate enhances atopic dermatitis-like skin lesions in mice

Di-(2-ethylhexyl) phthalate (DEHP) has been widely used in polyvinyl chloride products and has become ubiquitous in the developed countries. DEHP reportedly displays an adjuvant effect on immunoglobulin production. However, it has not been elucidated whether DEHP is associated with the aggravation of atopic dermatitis. We investigated the effects of DEHP on atopic dermatitis-like skin lesions induced by mite allergen in NC/Nga mice. NC/Nga male mice were injected intradermally with mite allergen on their right ears. In the presence of allergen, DEHP (0, 0.8, 4, 20, or 100 microg) was administered by intraperitoneal injection. We evaluated clinical scores, ear thickening, histologic findings, and the protein expression of chemokines. Exposure to DEHP at a dose of 0.8-20 microg caused deterioration of atopic dermatitis-like skin lesions related to mite allergen; this was evident from macroscopic and microscopic examinations. Furthermore, these changes were consistent with the protein expression of proinflammatory molecules such as macrophage inflammatory protein-1alpha (MIP-1alpha) and eotaxin in the ear tissue in overall trend. In contrast, 100 microg DEHP did not show the enhancing effects. These results indicate that DEHP enhances atopic dermatitis-like skin lesions at hundred-fold lower levels than the no observed adverse effect level determined on histologic changes in the liver of rodents. DEHP could be at least partly responsible for the recent increase in atopic dermatitis.     

Synergistic Effects of Korean Red Ginseng Extract and the Conventional Systemic Therapeutics of Atopic Dermatitis in a Murine Model

The synergistic effects of Korean Red ginseng (KRG, Panax ginseng C.A. Mey.) on conventional systemic therapeutics of atopic dermatitis (AD) have not been studied yet. To analyze the synergistic effects of KRG extract and the conventional systemic therapeutics of AD in TNCB-induced AD mouse model, we determined the change in modified scoring of index, the transepidermal water loss, the skin pathology, serum IgE, and the expression of various cytokines after combination treatment to the five-week-old NC/Nga female mice. The severity of AD was significantly decreased in the KRG + hydroxyzine (AH) group than AH group, and in the KRG + evening primrose oil (EPO) group than EPO group. A significant decrease in dermal inflammation was observed in the KRG + AH group than that in the AH group, and in the KRG + EPO group than that in the EPO group (p = 0.008), respectively. A decrease in CD1a expression was observed in the KRG + AH group when compared to the AH group (p = 0.008), and KRG + EPO group when compared to the EPO group. Compared to the CS group, the KRG + CS group showed a significant decrease in IL-17 expression. A combination of KRG and conventional systemic therapeutics can safely and effectively manage the AD.     

Influence of adjuvant-active peptidoglycan monomer on specific T cell responses in mice

Peptidoglycan monomer (PGM) originating from Brevibacterium divaricatum is a non-toxic, non-pyrogenic, water-soluble immunostimulator. It potentiates humoral immune response to ovalbumin (OVA) in mice upregulating both immunoglobulin (IgG) 1 and IgG2a antibody subclasses. This study concerns the influence of PGM on T cell activation and cytokine networks in response to OVA. OVA-specific proliferative response as well as interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) secretion in lymph node cell cultures of immunised mice were studied. Due to pharmacokinetic properties of PGM, namely its fast metabolism and excretion, special emphasis was on choosing the appropriate time for lymph node removal and duration of cell cultivation for each cytokine. PGM treatment in addition to OVA resulted in an increase of lymph node cellularity, stimulation of OVA-specific IFN-gamma and IL-4 production as well as of OVA-specific proliferative response. Results demonstrate that PGM stimulated both Th1 and Th2 subpopulations.