Serum cytokines and growth factor levels in Japanese patients with psoriasis

Background. Although the precise pathomechanism of psoriasis is still unknown, various cytokines and growth factors derived from T cells, dendritic cells or keratinocytes, are critically involved in this disease. There have been several studies determining the serum levels of cytokines in patients with psoriasis, but with conflicting results. The levels of various cytokines and growth factors were measured in the sera of patients with psoriasis and compared with those of healthy controls. The correlation with disease severity was also determined. Methods. Sera were collected from 122 patients with psoriasis and 78 healthy controls for ELISA analysis to evaluate the levels of cytokines and growth factors. The severity of psoriasis was determined by the Psoriasis Area and Severity Index (PASI). Results. Serum levels of tumour necrosis factor (TNF)‐α, interferon (IFN)‐γ, interleukin (IL)‐2, IL‐6, IL‐7, IL‐8, IL‐12, IL‐17, IL‐18 and vascular endothelial growth factor (VEGF) were significantly increased in patients with psoriasis compared with those of healthy controls. The serum levels of IL‐2, soluble intercellular adhesion molecule‐1, epidermal growth factor, hepatocyte growth factor and amphiregulin were not significantly different from those of healthy controls. Increased serum levels of TNF‐α, IFN‐γ, IL‐12, IL‐17, IL‐18 and VEGF correlated with PASI. Furthermore, these cytokine levels were decreased after psoriasis treatment. In contrast, serum levels of IL‐10 were decreased in psoriasis and negatively correlated with PASI. Discussion. Serum levels of TNF‐α, IFN‐γ, IL2, IL‐6, IL‐7, IL‐8, IL‐12, IL‐17, IL‐18 and VEGF were positively correlated and that of IL‐10 was negatively correlated with PASI in Japanese patients with psoriasis. These parameters might be useful for determining the disease activity of psoriasis.     

Relationship between serum levels of interleukin-18, IgE and disease severity in patients with atopic dermatitis

Background. Interleukin (IL)‐18 is a pleiotropic cytokine. Synergistically with IL‐12, IL‐18 promotes immune responses of the T helper type, by enhancing synthesis of interferon‐γ and inhibiting IgE production. IL‐18 can also enhance production of IL‐4 and IL‐13 production, and stimulate synthesis of IgE. Moreover, in the presence of IL‐3, IL‐18 can directly stimulate basophils and mast cells to produce their mediators in an IgE‐independent manner. These results indicate a role for IL‐18 in the pathogenesis of atopic dermatitis (AD). Aim. To examine the association of serum IL‐18 with IgE levels and disease severity in patients with AD. Methods. ELISA was used to measure IL‐18 and total IgE levels in the sera of 67 patients with AD and 50 healthy volunteers. The SCORing Atopic Dermatitis (SCORAD) tool was used to determine the severity of this disease. Results. The mean serum level of IL‐18 in study group (155.68 pg/mL) was significantly higher than that of controls. IL‐18 was also significantly higher in the sera of the patients with severe AD than in those with milder disease. There was a correlation with IgE and IL‐18 levels, as patients who had high IgE levels also had high IL‐18 levels, compared with controls. Conclusion. IL‐18 seems to play an important role in the pathogenesis of AD, but this requires further study. IL‐18 could be a useful clinical marker of disease severity in AD.     

Characteristics of extrinsic vs. intrinsic atopic dermatitis in infancy: correlations with laboratory variables

BACKGROUND: Atopic dermatitis (AD) has been divided into the extrinsic type (ADe) and the intrinsic type (ADi) according to the serum IgE levels and the presence or absence of allergen-specific IgE. Although previous studies have demonstrated differences in the various immunological parameters, the characteristics of AD in infancy have rarely been reported. OBJECTIVES: Our study was performed to analyse the correlations between the laboratory parameters of infantile ADe and ADi. METHODS: We recruited 237 infants with AD and checked the SCORAD index, the number of peripheral blood eosinophils, the serum eosinophil cationic protein (ECP) levels, the total serum IgE levels and the specific serum IgE levels in all the patients. We also checked the serum interleukin (IL)-4 and IL-5 levels in 20 patients with ADe and in 20 with ADi. RESULTS: This study showed many peculiar characteristics of infantile AD. In infancy, ADi was more prevalent than ADe. The eosinophil count, the ECP level and the SCORAD in ADi were lower than in ADe. Furthermore, a group of patients without characteristics of ADi or ADe could be identified. We tentatively classify this group as indeterminate type (ADind) and propose it as a separate entity. The clinical severity was well correlated with the eosinophil count and the serum ECP levels in ADe and ADi. Therefore these two parameters could be used as clinical severity markers in infancy. Infants are more allergic to food, and the variety of specific allergenic responses was connected with clinical severity. A higher eosinophil count, a higher ECP level and a higher detection rate of IL-5 in the peripheral blood of infants with ADe means that eosinophils have a more prominent role in ADe than in ADi. CONCLUSIONS: Infantile AD has many distinctive features in its laboratory variables as compared with AD in other age groups. Clinicians should recognize these facts when they deal with infants with AD, and further studies are warranted on the natural course of infantile AD.     

Interleukin-18 is elevated in the horny layer in patients with atopic dermatitis and is associated with Staphylococcus aureus colonization

Background An increase in interleukin (IL)‐18 production from epidermal cells has been reported in an atopic dermatitis (AD) mouse model, and subsequent topical application of Staphylococcus aureus results in severe dermatitis. Objectives To reveal the relationship between S. aureus colonization of skin lesions and keratinocyte IL‐18 production, particularly in AD with relatively low serum IgE levels. We also aimed to establish a simple and noninvasive method of assaying IL‐18 produced by epidermal keratinocytes to evaluate local skin inflammation and therapeutic effects in patients with AD. Methods IL‐18 in the horny layer of the skin was collected via a tape‐stripping method and measured in 95 patients with AD and 40 healthy controls by enzyme‐linked immunosorbent assay (ELISA). Clinical severity, blood data and S. aureus skin colonization were evaluated before and after treatment. Results IL‐18 levels in the horny layer were significantly higher in the skin lesions of patients with AD than in healthy controls and correlated with SCORAD, levels of serum IL‐18, IgE, lactate dehydrogenase, thymus and activation‐regulated chemokine, blood eosinophils and transepidermal water loss. In the AD group with serum IgE < 1500 IU mL^?1, significantly higher IL‐18 levels were observed in the horny layer of patients colonized with S. aureus compared with those who were not. Conclusions Epidermal IL‐18 production was associated with the severity of AD. Staphylococcus aureus colonization seems to contribute to this IL‐18 production, especially in the AD group with relatively low IgE production. Tape stripping provides an easy and noninvasive method to assess epidermal IL‐18 production by ELISA.     

Serum eosinophil cationic protein in children with atopic dermatitis

BACKGROUND: Eosinophil cationic protein (ECP) is a cytotoxic agent secreted by activated eosinophils during allergic and inflammatory processes. The aim of the study was to determine the ECP level, absolute and relative eosinophil count and IgE antibodies in children with atopic dermatitis (AD) compared with those of nonatopic children, and to assess the correlation of these laboratory parameters with the clinical severity of AD. METHODS: This prospective study comprised 70 children. There were 49 children with AD aged 3-36 months, and the control group comprised 21 children with a negative personal and family history for atopic diseases. Detailed history, serum ECP levels (UniCAP FEIA), relative and absolute eosinophil counts and total serum IgE antibodies were determined in both groups. In the children with AD, skin involvement was measured by the SCORAD index. RESULTS: The calculated SCORAD index was between 16 and 83. IgE antibodies, relative and absolute eosinophil counts showed a significantly wider range of values and a statistically higher median (P < 0.001) in the patients with AD compared with the control group. These laboratory parameters did not correlate with the severity of AD. The serum ECP median level, in the children with AD, was 16.2 microg/L (range 3.01-65.30) compared with 5.92 microg/L (range 2.76-21.90) in the control group. Correlation of the total SCORAD index and the serum ECP levels was negative, weak (r = -0.065) and statistically not significant (P > 0.05). The same was found for the correlation of serum ECP and intensity of skin changes (r = -0.095) and serum ECP and subjective symptoms (r = -0.045). The correlation was positive, but weak and statistically not significant for the serum ECP and extent of the skin lesions (r = 0.079, P > 0.05). CONCLUSION: Elevated levels of ECP, relative and absolute eosinophil counts, as well as IgE antibodies were determined in the patients with AD. As these laboratory findings did not correlate with the severity of AD, they can be considered only as additional methods in the evaluation of patients with AD.     

Serum measurement of interleukin‐31 (IL‐31) in paediatric atopic dermatitis: elevated levels correlate with severity scoring

Background Interleukin‐31 (IL‐31) is a novel T‐helper‐lymphocyte‐derived cytokine that plays an important role in human T‐cell‐mediated skin diseases. When overexpressed in transgenic mice, IL‐31 induces severe pruritus resembling eczema in humans. Serum IL‐31 was previously found overexpressed in adults with atopic dermatitis (AD). The novelty of this study is the use of a pediatric patient group as well as comparison of IL‐31 levels during flare and quiescence. Objective This case‐controlled longitudinal study was designed to determine the levels of IL‐31 in serum of AD children and its associations in relation to disease activity and severity. Methods Sera were obtained from 50 AD children and 40 healthy volunteers. IL‐31 levels were measured using a sandwich ELISA. All AD patients were followed up and re‐sampled for serum IL‐31 after clinical remission. Serum IL‐31 levels were correlated with AD disease activity and severity variables. Results Serum IL‐31 levels were significantly higher whether during AD flare [median, 1600; mean (SD) = 1457.8 ± 770.4 pg/mL] or quiescence (1040; 958.7 ± 419.5 pg/mL), than those in controls (220; 197.3 ± 91.9 pg/mL). Serum IL‐31 levels were significantly higher in the high disease severity group compared with the moderate or low severity group. Moreover, serum IL‐31 levels correlated positively with the calculated severity scores (LSS, SSS and SCORAD index). Conclusion The results of this study confirm the importance of IL‐31 in AD pathophysiology. Serum IL‐31 level is an objective reliable marker of AD severity in children. It may represent a novel target for antipruritic drug development.     

Full-spectrum light phototherapy for atopic dermatitis

Background Atopic dermatitis (AD) is a chronic skin disease resulting in a profound deterioration in quality of life. The FSL^® is a newly developed phototherapy device generating full‐spectrum light (FSL) with a continuous wavelength (320–5000 nm). This study aimed to evaluate the efficacy and safety of FSL^® phototherapy in AD. Methods We enrolled 38 patients with moderate to severe AD in this open, randomized, controlled, prospective study. In the FSL‐irradiated group (20 patients), irradiation was conducted twice per week for 4 consecutive weeks. In the control group (18 patients), only emollient application was allowed. SCORing Atopic Dermatis (SCORAD) values were obtained at baseline, week 4 and 8. Patients were asked to give subjective assessments of improvement and laboratory tests including serum eosinophil counts, ECP levels, IgE levels and 22 cytokine levels were performed. Results In the FSL‐irradiated group, the mean SCORAD value decreased significantly after 4 weeks of phototherapy and remained reduced for a further 4 weeks after the cessation of treatment. In the control group, the mean SCORAD value did not change significantly over the study period. Patients’ subjective assessments indicated good to excellent responses in 75% of the FSL‐irradiated group, by contrast with 50% of the control group. The mean values for serum eosinophil counts, IL‐4 and IL‐5 levels decreased significantly after FLS phototherapy. No serious adverse effects were reported. Conclusions In this study, we showed that FSL^® phototherapy can be an effective and safe treatment option in AD.     

Vitamin D Level in Children Is Correlated with Severity of Atopic Dermatitis but Only in Patients with Allergic Sensitizations

Vitamin D is believed to affect the progression and severity of atopic dermatitis (AD). Allergic sensitization may cause this effect to vary. Individuals who fulfilled the Hanifin and Rajka criteria for AD underwent epidermal prick tests and blood tests for specific immunoglobulin E(IgE), serum total IgE, 25‐hydroxy vitamin D, and peripheral blood eosinophil count and percentage. Disease severity was determined according to the Scoring Atopic Dermatitis (SCORAD) index. Patients were grouped according to allergic sensitization. Seventy‐three children with AD (median age 33.0 mos, interquartile range 19.0–61.5 mos) were enrolled in the study; 33 (45.2%) were found to have allergic sensitization. In this group there was a negative correlation between SCORAD score and serum vitamin D level (p = 0.047, correlation coefficient [r] = ?0.349), whereas there was no correlation in the group without sensitization (p = 0.30, r = ?0.168). Vitamin D was not correlated with total IgE and eosinophil percentage in either AD group (p = 0.77, r = 0.054 and p = 0.73, r = ?0.062, respectively). Vitamin D may affect the severity of AD, especially in children with allergic sensitization.     

14~55岁特应性皮炎患者严重程度与维生素D、总IgE和嗜酸性粒细胞的相关性

目的探究青少年及成人特应性皮炎患者疾病严重程度与血清25-羟基维生素D、总IgE和嗜酸性粒细胞计数的相关性。方法参考SCORAD评分法评估112例青少年及成人特应性皮炎患者疾病严重程度,并检测患者及70例健康组血清25-羟基维生素D水平以及患者总IgE、嗜酸性粒细胞数计数。结果特应性皮炎组患者血清25-羟基维生素D水平(20.42±6.96)ng/mL明显低于健康组(28.68±7.85)ng/mL,差异有统计学意义(P=0.000<0.01)。重度患者血清25-羟基维生素D水平(18.93±7.06)ng/mL低于轻中度患者(21.62±6.70)ng/mL,差异有统计学意义(P=0.041<0.05);重度患者总IgE水平(5184.08±7533.82)IU/mL明显高于轻中度患者(1075.07±1777.37)IU/mL,差异有统计学意义(P=0.000<0.01);重度患者嗜酸性粒细胞计数升高(37/50)的比例明显高于轻中度患者(17/62),差异有统计学意义(P=0.000<0.01);血清25-羟基维生素D、总IgE、嗜酸性粒细胞计数均与SCORAD评分相关。结论青少年及成人特应性皮炎患者的血清25-羟基维生素D水平较健康人明显偏低,且与病情严重程度呈负相关;总IgE、嗜酸性粒细胞计数与病情严重程度呈正相关。     

Serum cytokine levels in atopic dermatitis

Elevated IgE responses and eosinophilia observed in patients with atopic dermatitis (AD) may reflect increased responses of type 2 T-helper (Th2) cytokines with a concomitant decrease in interferon-gamma (IFN-gamma) production. However, the cross-regulation of Th1/Th2 derivation and function in AD patients are incompletely characterized. Therefore, we investigated serum levels of several cytokines [interleukin (IL)-18, IL-12, IL-10, IL-2 and IFN-gamma] in patients with AD to assess their possible relationships to the severity of disease. Serum IL-18 levels in AD patients were significantly higher than those in healthy controls [207 pg/mL; 95% confidence interval (CI), 172-242 pg/mL vs. 144 pg/mL; 95% CI, 116-178 pg/mL; P = 0.026]. Those IL-18 levels significantly correlated with eosinophil counts and serum soluble IL-2 receptor (sIL-2R) levels, and showed a tendency to correlate with clinical severity scores and serum IgE levels. IL-2 levels showed a significantly inverse correlation with serum IgE levels, and IL-12 levels clearly correlated with IL-10 levels. These results suggest the value of serum IL-18 levels as a parameter of AD activity and may support a possible role for IL-18 in the pathogenesis of AD. The inverse correlation between IgE levels and IL-2 levels suggests that IgE production may be inhibited by IL-2 in patients with AD. Furthermore, the correlation of IL-12 levels with IL-10 levels may support the previous reports that show the induction of IL-10 production by human natural killer cells and/or T cells stimulated with IL-12 in vitro.     

Effect of Probiotics on the Treatment of Children with Atopic Dermatitis

Background

Atopic dermatitis, a chronic recurrent disease, is frequently encountered in clinical practice. In the last 30 years, the prevalence of atopic dermatitis has rapidly increased due to industrialization. Therefore, there have been attempts in recent years to find new ways of treating and preventing atopic dermatitis.

Objective

In this double-blind, randomized, placebo-controlled study, a combination of Bifidobacterium bifidum, Lactobacillus acidophilus, Lactobacillus casei, and Lactobacillus salivarius strains were evaluated in the treatment of atopic dermatitis in pediatric patients.

Methods

Forty pediatric patients (23 males and 17 females) aged 1~13 years were enrolled. One eligible individual who was approached declined to participate. The probiotic group was administered a probiotic complex containing B. bifidum, L. acidophilus, L. casei, and L. salivarius for 8 weeks. The placebo group, on the other hand, was administered skim milk powder and dextrose. All of the parameters including serum cytokines, eosinophil cationic protein), SCORing Atopic Dermatitis (SCORAD) index, and total serum immunoglobulin E (IgE) were measured in both the probiotic group and the placebo group at the end of 8 weeks.

Results

Probiotic intervention in pediatric atopic dermatitis patients effectively reduced the SCORAD index and serum cytokines interleukin (IL)-5, IL-6, interferon (IFN)-γ, and total serum IgE levels, but did not reduce levels of serum cytokines IL-2, IL-4, IL-10, ECP, or tumor necrosis factor-α (TNF-α) compared to the placebo group.

Conclusion

Our study found probiotics to be effective in reducing atopic dermatitis patients'' SCORAD index, serum IL-5, IL-6, IFN-γ, and total serum IgE levels but not effective in reducing serum IL-2, IL-4, IL-10, ECP, or TNF-α levels.     

Soluble E-selectin, other markers of inflammation and disease severity in children with atopic dermatitis

E-selectin, P-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are membrane-bound adhesion molecules which mediate the attachment of leucocytes to endothelial cells. These molecules are preferentially expressed on activated endothelium. The soluble forms of these molecules (sE-selectin, sP-selectin, sICAM-1 and sVCAM-1) are present in the circulation as a result of shedding. Some of the soluble adhesion molecules have been thought to reflect disease activity in atopic dermatitis (AD). To evaluate their potential to reflect disease activity in AD, we correlated their plasma concentration with clinical severity measured by objective SCORAD (SCORing Atopic Dermatitis). Furthermore, levels of total IgE, specific IgE, and eosinophil cationic protein (ECP) were determined. SCORAD and sE-selectin levels were significantly increased in children with specific IgE for both food and inhalation allergens ( P  < 0.05). ECP consistently showed an increase with the scores of SCORAD, but no statistical significance was reached. Disease activity was significantly correlated with the plasma levels of sE-selectin ( r _s = 0.6, P  < 0.0005) but not with sP-selectin, sICAM-1 and sVCAM-1. This agrees with recent studies performed in adults with AD, and supports the potential of sE-selectin as a parameter for monitoring disease activity in young children with AD.     

特应性皮炎患者血清转谷氨酰胺酶2特异性IgE水平与病情相关性研究

目的 检测特应性皮炎(AD)患者血清中转谷氨酰胺酶2(TG2)特异性IgE(sIgE)的表达水平,并分析与患者病情的相关性.方法 共入组77例AD患者,其中,44例≥12岁,33例＜12岁,内源性AD(特异性sIgE阴性,且总IgE＜150 kU/L)20例,外源性AD(一种以上的外源性过敏源sIgE++以上,或总IgE≥150 kU/L)49例.采用免疫捕获及生物素标记的酶联免疫分析法检测77例AD患者、40例成人寻常性银屑病患者和30例成人健康对照血清中TG2 sIgE水平.记录AD患者年龄、病程、SCORAD评分、嗜酸性粒细胞计数和总IgE及TG2的sIgE水平.结果 ≥12岁AD组、＜12岁AD组、银屑病组和对照组外周血TG2 sIgE水平(A450)分别为1.02±0.2、1.04±0.044、0.93±0.25、0.71±0.13.≥12岁AD、寻常性银屑病和健康对照组外周血中TG2 sIgE表达水平差异有统计学意义(x2=37.407,P＜0.001);两两组间比较发现,≥12岁AD组、银屑病组TG2 sIgE水平均显著高于对照组(t值分别为7.38、4.83,均P＜0.001).内源性AD组TG2 sIgE水平(1.16±0.03)高于外源性AD组(1.02±0.20)(t=2.27,P=0.02).AD患者组TG2 sIgE水平与年龄、病程、SCORAD评分、嗜酸性粒细胞计数、血清总IgE水平均无显著相关性(r值分别为0.03、0.14、-0.04、-0.08和0.06,均P＞0.05).结论 AD患者血清中TG2 sIgE水平明显升高,TG2可能是AD患者的一种自身抗原,但TG2 sIgE与患者的病情严重程度无明显相关性.     

Association of serum interleukin-18 and other biomarkers with disease severity in adults with atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin for which there are no reliable biomarkers to assess clinical severity. Serum interleukin-18 (IL-18) levels may be associated with AD severity. To identify putative biomarkers associated with clinical severity in adult AD patients, we enrolled 121 adult AD patients (mean age 35.7 years) and 50 healthy controls (mean age 31.7 years). We compared these groups for blood eosinophils and serum levels of IL-18, thymus and activation-regulated chemokine (TARC), total IgE, and lactate dehydrogenase (LDH). We also determined S. aureus enterotoxin B (SEB) specific IgE levels and the SCORingAD (SCORAD) scores for AD patients. For AD patients, stepwise logistic regression was used to estimate odds ratios (OR) for each biomarker for the likelihood of having AD, and multiple linear regression was used to identify biomarkers associated with SCORAD scores. Compared with healthy controls, adult AD patients had higher levels of IL-18, TARC, total IgE, eosinophils, and LDH. TARC levels had the highest OR for AD occurrence, while the OR for IL-18 was insignificant. Also, IL-18 was not related to the presence of SEB-IgE. Notably, IL-18 levels were significantly associated with SCORAD scores, as were TARC, total IgE, and LDH levels. A panel of biomarkers (IL-18, TARC, total IgE, and LDH) may be more useful to accurately assess clinical severity in adult AD patients.     

Significance of interleukin-16, macrophage-derived chemokine, eosinophil cationic protein and soluble E-selectin in reflecting disease activity of atopic dermatitis--from laboratory parameters to clinical scores

BACKGROUND: The search for the ideal clinical score reflecting atopic dermatitis (AD) severity has developed in parallel with unveiling key events in disease pathogenesis and finding laboratory parameters for monitoring disease activity. A major difficulty in assessing the relevance of reported serum markers of AD severity is the use of nonvalidated referent tools, which compromises comparison of results across studies. OBJECTIVES: The aim of our study was to compare the significance of serum levels of interleukin (IL)-16, macrophage-derived chemokine (MDC), soluble E-selectin (sE-selectin) and eosinophil cationic protein (ECP) in reflecting AD severity and identify the most relevant parameter for monitoring the course of disease. Serum levels were tested against the same referent severity score in the same time frame and group of patients. METHODS: The Severity Scoring of Atopic Dermatitis (SCORAD) index was used for assessment of disease severity in 21 adult patients in acute stage of AD and after complete resolution of clinical findings. Serum levels of IL-16, MDC, ECP and sE-selectin were measured at the same time points in 18 patients and compared with healthy nonatopic controls. The correlation between SCORAD and each laboratory parameter was tested for significance and compared. RESULTS: Serum levels of IL-16, MDC, ECP and sE-selectin were significantly higher in patients in acute stage of AD compared with controls and decreased significantly after treatment, in parallel with clinical improvement. All monitored parameters reflected disease severity assessed by the clinical score. We found the highest significance level of correlation with SCORAD for IL-16 (r = 0.68, P =0.0019), followed by ECP (r = 0.65, P = 0.0032) and MDC (r = 0.55, P =0.0326). There was significant correlation between serum levels of IL-16 and MDC (r = 0.53, P = 0.0443) and ECP and sE-selectin (r = 0.48, P = 0.0427). CONCLUSIONS: The study established a significant correlation between serum levels of IL-16 and SCORAD in adult AD patients. We report a significant correlation between IL-16 and MDC, both T-helper 2 activation markers. Our data suggested that IL-16 reflects most convincingly disease severity and may be used as a marker in clinical studies preferentially in combination with a clinical activity score.     

Reduction of serum interleukin-5 levels reflect clinical improvement in patients with atopic dermatitis.

Cytokines, in particular IL-4 and IL-5, regulate IgE synthesis and eosinophil activation in atopic dermatitis (AD). To elucidate whether the serum levels of IL-4 and IL-5 are related to the serum IgE level, eosinophilia, or clinical severity of the disease, 25 cases with AD were studied. Blood samples were isolated from two groups of donors: 1) patients with AD (n = 25); 2) non-allergic individuals (NA, n = 20) with serum IgE levels below 100 IU/ml and with blood eosinophil counts below 250/microliter. Each parameter was evaluated at least twice in AD patients at the beginning of the study and after 4, 8 or 12 weeks of treatment. IL-4 was hardly detected in AD and NA, but IL-5 was increased (> 10 pg/ml) in most cases (22/25) of AD group with 513.6 pg/ml as the mean. AD with normal serum IgE levels exhibited increased levels of IL-5, whereas AD with high serum IgE levels did not necessarily have elevated IL-5 levels. The IL-5 level tended to change in parallel with the clinical severity in each AD case, although the level itself was not correlated with the clinical severity per se. A significant decrease of IL-5 was observed in AD when the clinical severity decreased. Eosinophils also decreased along with the improvement of AD, whereas the serum level of IgE did not change during the observation period. Our results suggest that IL-5 is involved in the regulation of clinical courses of AD and that its kinetics at the serum level reflects the clinical activity of AD.     

Genetic predisposition to parthenium dermatitis in an Indian cohort due to lower-producing genotypes of interleukin-10 (-) 1082 G>A and (-) 819 C>T loci but no association with interferon-γ (+) 874 A>T locus

Summary Background Parthenium dermatitis is an activated T cell‐mediated type IV hypersensitivity. Its pathogenesis is well characterized, with interindividually varying serum levels of pro‐ and anti‐inflammatory and regulatory T‐cell cytokines and coherently perturbed cross‐regulation between them. The functional single nucleotide polymorphisms (SNPs) in these cytokine genes might function as risk/susceptibility factors for the disease. Objectives We analysed the serum levels of interferon (IFN)‐γ and interleukin (IL)‐10 cytokines in cases vs. controls and investigated whether IFN‐γ (+) 874 A>T and IL‐10 (?) 1082 G>A and (?) 819 C>T are associated with serum levels and genetically predispose to the disease. Methods The study included 60 patch test‐confirmed patients and 60 age‐ and sex‐matched controls. The serum levels of cytokines were estimated by high‐sensitivity enzyme‐linked immunosorbent assay kits. SNP genotyping was performed by amplification refractory mutational system–polymerase chain reaction. Results In patients, the serum level of IFN‐γ was significantly increased and that of IL‐10 was significantly decreased, with no difference in IgE concentration. Genetically no IFN‐γ (+) 874 A>T alleles/genotypes were associated with the disease, but a strong predisposition was found due to lower‐producing genotypes of IL‐10 (?) 1082 G>A and (?) 819 C>T SNPs, with 2·1 and 3·5 times more risk, respectively, while intermediate IL‐10‐producing genotypes provided resistance. Conclusions High serum IFN‐γ might play a role in disease pathogenesis, but this is genetically not endowed by the IFN‐γ SNP studied. In contrast, low serum IL‐10 was very much connected, with the genetics of both studied IL‐10 loci. These might be key managing factors concerning pathogenesis/susceptibility.     

Effect of topical application and intraperitoneal injection of oregonin on atopic dermatitis in NC/Nga mice

Please cite this paper as: Effect of topical application and intraperitoneal injection of oregonin on atopic dermatitis in NC/Nga mice. Experimental Dermatology 2010; 19 : e37–e43. Abstract: The diarylheptanoid, oregonin (ORE), which was isolated from the bark of Alnus japonica Steudel that grows natively in Korea, has been known to exert antioxidative, anti‐inflammatory, anti‐cancer and immune response inhibitory effects. The antioxidative effect of ORE was observed on the superoxide and 1,1‐diphenyl‐2‐picrylhydrazyl radical, as well as on the expression of inducible nitric oxide synthase and cyclooxygenase‐2 in lipopolysaccharide‐treated RAW264.7 macrophages. The statistically significant inhibitory action of ORE against production of cytokines induced by bacterial products or by interleukin (IL)‐1β, free radicals and nitrogen species, and a corresponding increase in cellular calcium concentration because of ORE were confirmed in bone marrow and spleen dendritic cells that are known to play important functions in the development and advancement of atopic dermatitis (AD). It was thus expected that ORE would exert a beneficial effect in the treatment of AD. A study on the pharmaceutical benefits of ORE against AD has not yet been conducted in vivo. We therefore used an in vivo AD animal model, namely the NC/Nga mice, and by applying ORE onto the animals through skin application as well as intraperitoneal injection, we attempted to evaluate the benefits of ORE in this system. Evaluation of ORE was conducted by following the SCORE method to score the effect, as well as by measuring the Th2 cytokines IL‐4, IL‐5 and IL‐13 levels from serum and lymphocytes, and IgE and eosinophil levels from serum. Additionally, the expression of mRNA and protein levels was estimated using real‐time polymerase chain reaction and Western blotting analysis. The following categories of clinical evaluation, Th2 cytokines IL‐4, IL‐5 and IL‐13 values, serum IgE levels, serum eosinophil levels, and mRNA and protein expression levels of iNOS and COX‐2, were evaluated from topical application and intraperitoneal injection groups of ORE. The effects of ORE on AD in NC/Nga mice were confirmed as being similar to the positive control group, while a significant difference with the negative control group was observed. The results presented in this report suggest that ORE might be beneficial in the treatment of AD.     

Effects of CO2 fractional laser therapy on peripheral blood cytokines in patients with vitiligo

Vitiligo is a disease pathologically characterized by specific damage to melanocytes. The aim of this study was to explore the mechanism underlying CO2 fractional laser treatment of vitiligo by detecting the levels of Th1 cytokines (IL‐2 and IFN‐γ), Th2 cytokines (IL‐4 and IL‐10), and Th17 cytokines (IL‐17 and IL‐23) in peripheral blood. Twenty five vitiligo patients were enrolled in this study and were treated with a CO2 fractional laser four to eight times. The cytokines of 25 vitiligo patients and 20 healthy volunteers were measured by enzyme‐linked immunosorbent assay. After CO2 fractional laser therapy, six cases were cured, and the apparent efficiency was 72.0% (18/25), while the efficiency was 92.0% (23/25). Before CO2 fractional laser therapy, IL‐2 and IFN‐γ levels in vitiligo patients were higher than those in the control group, but the difference was not statistically significant (p > .05). IL‐4, IL‐10, IL‐17, and IL‐23 levels were also higher in vitiligo patients than those in the control group (p < .05). After treatment, IL‐2 and IFN‐γ levels in vitiligo patients were lower than before treatment, but the difference was not statistically significant (p > .05), while IL‐4, IL‐10, IL‐17, and IL‐23 levels were significantly lower compared with before treatment (p < .05). The results show that CO2 fractional laser treatment has a good curative effect in the treatment of vitiligo.