利多卡因对金黄色葡萄球菌外毒素TSST-1刺激的特应性皮炎患者外周血单一核细胞的影响

目的 探讨利多卡因对金黄色葡萄球菌外毒素激活特应性皮炎患者单一核细胞的影响。 方法 抽取6例特应性皮炎患者外周血,常规分离培养单一核细胞。以金黄色葡萄球菌外毒素刺激共孵育,同时加入不同浓度的利多卡因。3H-TdR掺入法检测单一核细胞增殖,酶联免疫吸附法（ELISA）检测Th1 和Th2细胞因子的释放。Western印迹法检测利多卡因对与中毒性休克综合征毒素1（TSST-1）刺激的特应性皮炎患者单一核细胞共孵育的HaCaT细胞中间丝相关蛋白的表达。 结果 TSST-1（100 μg/L）显著刺激了特应性皮炎患者单一核细胞的增殖（SI = 75 ± 2.12,P < 0.05）,并刺激α肿瘤坏死因子、γ干扰素、白细胞介素（IL）2、IL-12、IL-4、IL-5、IL-13细胞因子的释放（均P < 0.05）。CCK-8检测结果显示,与空白对照组相比,100 μmol /L利多卡因显著抑制了TSST-1刺激的特应性皮炎患者单一核细胞的增殖（SI = 58 ± 3.14,P < 0.05）,亦显著抑制了TSST-1刺激的特应性皮炎患者外周血IL-4、 IL-5、 IL-13、α肿瘤坏死因子以及γ干扰素的释放,差异有统计学意义（均P < 0.05）。Western印迹法结果显示,100 μmol/L利多卡因阻断了HaCaT细胞中间丝相关蛋白表达的下调,差异有统计学意义（P < 0.01）。 结论 利多卡因对TSST-1刺激的特应性皮炎患者单一核细胞的激活具有明显的抑制作用。     

特应性皮炎患者外周血外泌体调控HaCaT细胞活化及炎症的研究

目的：明确特应性皮炎（AD）患者外周血中外泌体对角质形成细胞(KC)的活化及炎症的影响。方法：检测我院AD患者和健康人的外周血样本并分离血浆中外泌体，每组各30例。首先将0 g/L、20 g/L、40 g/L、80 g/L蛋白浓度的正常人-外泌体分别与人角质形成细胞系HaCaT细胞共培养，采用CCK-8法检测各组细胞的增殖情况，采用Annexin V-FITC/PI双染法检测各组细胞的凋亡情况，确定外分泌体最佳实验浓度。然后将最佳浓度的外泌体与AD患者KC细胞共培养，利用荧光定量-PCR检测AD-外泌体组、正常人-外泌体组和空白对照组细胞的活化（K16）、分化（K10、IVL）、炎症指标（TSLP、IL-25、IL-33、CXCL1、CXCL2）。结果：较其他浓度，40 g/L浓度下正常人-外泌体的HaCaT细胞增殖率最低，凋亡率最高，为最佳实验浓度。与对照组和正常人-外泌体组比较，AD-外泌体组中K16、K10、IVL、TSLP、IL-25、IL-33、CXCL2表达上调（P<0.05），CXCL1表达水平无统计学差异（P>0.05）。结论：AD患者外周血外泌体可以促进KC的分化、活化及炎症因子的分泌，从而参与AD的发生发展。     

进行性斑状色素减少症发病机制初步探讨

目的探讨进行性斑状色素减少症(progressive macular hypomelanosis,PMH)患者皮损中分离出的痤疮丙酸杆菌对人角质形成细胞(human keratinocytes,HaCaT)细胞分泌干扰素(interferon,IFN)-γ、白细胞介素(interleukin,IL)-6、肿瘤坏死因子(tumor necrosis factor,TNF)-α的影响。方法体外培养HaCaT细胞株,分别加入分离自PMH的痤疮丙酸杆菌、痤疮丙酸杆菌标准菌株(NCTC737),酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)方法测定细胞上清液中IFN-γ、IL-6、TNF-α的分泌量。结果 PMH患者中分离的痤疮丙酸杆菌与角质形成细胞HaCaT细胞株共培养后,能促进角质形成细胞分泌IFN-γ和IL-6,与空白组比较,有明显升高,差异有统计学意义(P0.05);与痤疮丙酸杆菌标准菌株NCTC737相比也升高,差异有统计学意义(P0.05)。结论进行性斑状色素减少症皮损中分离出的痤疮丙酸杆菌可刺激HaCaT细胞分泌IFN-γ、IL-6、TNF-α,提示可能是皮损色素减退的原因之一。     

Caspase抑制剂对特应性皮炎患者外周血CD4+T细胞亚群分泌细胞因子的影响

目的：明确广谱半胱氨酸天冬氨酸蛋白酶(caspase)抑制剂对特应性皮炎(AD)患者外周血CD4+T细胞亚群分泌细胞因子的影响。方法：广谱caspase抑制剂Z-VAD-FMK与30例AD患者外周血单一核细胞(PBMCs)体外共培养后,PBMCs分为3组,分别加入Z-VAD-FMK溶液、地塞米松溶液和PBS溶液。流式细胞仪检测CD4+T细胞亚群;ELISA方法检测上清液中IFN-γ、IL-4、IL-17的浓度。结果：IFN-γ、IL-4、IL-17水平在PBS溶液组高于Z-VAD-FMK组,差异均有统计学意义(均P<0.01),在Z-VAD-FMK组与地塞米松组间比较,均无统计学意义(均P>0.05)。结论：广谱caspase抑制剂Z-VAD-FMK可抑制AD患者PBMC中CD4+T细胞Th1、Th2、Th17分泌相关细胞因子。     

Atopic dermatitis in adults: evaluation of peripheral blood mononuclear cells proliferation response to Staphylococcus aureus enterotoxins A and B and analysis of interleukin-18 secretion

Background:  Atopic dermatitis (AD) is a chronic, inflammatory skin disease with a high prevalence and complex pathogenesis. The skin of AD patients is usually colonized by Staphylococcus aureus ( S. aureus ); its exotoxins may trigger or enhance the cutaneous inflammation. Several mediators are related to the AD immune imbalance and interleukin-18 (IL-18), an inflammatory cytokine, may play a role in the atopic skin inflammation.
Aims:  To evaluate peripheral blood mononuclear cells (PBMC) proliferation response to staphylococcal enterotoxins A (SEA) and B (SEB) and the levels of IL-18 in adults with AD.
Methods:  Thirty-eight adult patients with AD and 33 healthy controls were analysed. PBMC were stimulated with SEA and SEB, phytohemaglutinin (PHA), pokeweed (PWM), tetanus toxoid (TT) and Candida albicans (CMA). IL-18 secretion from PBMC culture supernatants and sera were measured by ELISA.
Results:  A significant inhibition of the PBMC proliferation response to SEA, PHA, TT and CMA of AD patients was detected ( P  ≤ 0.05). Furthermore, increased levels of IL-18 were detected both in sera and non-stimulated PBMC culture supernatants from AD patients ( P  ≤ 0.05).
Conclusions:  A decreased PBMC proliferation response to distinct antigens and mitogens (TT, CMA, SEA and PHA) in adults with AD suggest a compromised immune profile. IL-18 secretion from AD upon stimulation was similar from controls, which may indicate a diverse mechanism of skin inflammation maintained by Staphylococcus aureus. On the other hand, augmented IL-18 secretion from AD sera and non-stimulated cell culture may enhance the immune dysfunction observed in AD, leading to constant skin inflammation.     

儿童特应性皮炎患者外周血单一核细胞IL-31与疾病严重程度相关性分析

目的 探讨IL-31在儿童特应性皮炎发病机制中的作用以及与特应性皮炎瘙痒的相关性。方法 22例特应性皮炎患儿与22例健康儿童外周血单一核细胞在葡萄球菌肠毒素B（SEB）刺激或非刺激状态下，应用实时PCR方法分析IL-31表达情况；酶联免疫吸附法测定其血清IgE水平；对患儿病情进行病情严重程度评分，分析IL-31 mRNA与IgE水平、疾病严重程度及瘙痒的相关性。结果 特应性皮炎患儿外周血单一核细胞IL-31表达显著增加，是对照组的23.2倍（P < 0.01）。特应性皮炎组和对照组外周血单一核细胞受SEB刺激后IL-31表达均有不同程度升高，以特应性皮炎组IL-31表达增加更显著，是对照组的20.44倍。患儿血清总IgE水平中位数为260.05 IU/mL（范围5.9 ～ 1131.01 IU/mL），对照组为17.7 IU/mL（范围5 ～ 140.7 IU/mL），两组比较，P < 0.01。IL-31与患儿病情严重程度以及血清总IgE水平无显著相关性（r = 0.07，P > 0.05；r = 0.22，P > 0.05）。结论 IL-31可能参与儿童特应性皮炎发病，其作用机制可能不依赖血清IgE；SEB能诱导正常人外周血单一核细胞快速表达IL-31，是IL-31产生的重要调节因素。     

Effects of two novel cationic staphylococcal proteins (NP-tase and p70)and enterotoxin B on IgE synthesis and interleukin-4 and interferon-gamma production in patients with atopic dermatitis

We have characterized the cell-mediated and humoral immune response of patients with atopic dermatitis (AD) and healthy controls in response to two novel staphylococcal antigens (NP-tase, p70) and the superantigen staphylococcal enterotoxin B (SEB). The parameters studied were IgE, interleukin (IL)-4 and interferon (IFN)-gamma synthesis by peripheral blood mononuclear cells (PBMC) after stimulation with NP-tase, p70 and SEB in vitro. Both antigens, as well as SEB, induced IL-4 and IFN-gamma secretion in patients and controls. However, patients with AD showed a significantly diminished IFN-gamma production in response to NP-tase or SEB. Furthermore, we demonstrated a good correlation between antigen-stimulated IgE production and the IL-4/IFN-gamma ratio in vitro. A distinct subgroup of PBMC showed impaired IFN-gamma synthesis and enhanced IL-4 secretion after incubation with p70 or NP-tase. These data support evidence that a subgroup of patients with AD, synthesizing low levels of IFN-gamma after stimulation with staphylococcal antigens, may have impaired abilities to clear Staphylococcus aureus colonization. Persistent staphylococcal antigens could then be responsible for inflammatory and allergic skin reactions in patients with AD. We therefore conclude that, besides superantigens, staphylococcal antigens may also play a part in the pathogenesis of AD.     

Enhanced TARC production by dust-mite allergens and its modulation by immunosuppressive drugs in PBMCs from patients with atopic dermatitis

BACKGROUND: Thymus and activation regulated chemokine (TARC) is a CC chemokine that attracts CCR4+ T cells. We reported previously that TARC is an important chemokine that defines Th2 imbalance in the pathogenesis of atopic dermatitis (AD). OBJECTIVES: This study was undertaken to clarify TARC producing cells in peripheral blood mononuclear cells (PBMCs), the regulation of dust mite-allergen clude extract (DME) and different immunosuppressive drugs (Tacrolimus (FK506), cyclosporine (CsA), dexamethasone (Dex)) on TARC production by peripheral PBMCs from AD patients in vitro. METHODS: Monocyte derived dendritic cells (MoDCs) were generated from and TARC mRNA levels were examined and comapared with those from T cells in PBMCs from AD patients. PBMCs were cultured with or without DME and/or immunosuppressive drugs (Tacrolimus, CsA, Dex) for 7 days and TARC levels were measured. RESULTS: PBMCs from AD patients which were cultured with DME stimulation for 7 days showed significantly higher levels of TARC production than those from healthy controls. RT-PCR demonstrated that TARC mRNA was expressed in CD4+ T cells, CD8+ T cells and MoDCs. Tacrolimus, CsA and Dex individually suppressed TARC production by PBMCs from AD patients which were co-cultured with DME for 7 days. Gel shift analysis revealed differential inhibitory effects of these immunosuppressive drugs on NFkappaB activity in PBMCs from AD patients. CONCLUSION: Our data demonstrate that TARC producing cells are MoDCs, T cells as well as epidermal keratinocytes in AD. We suggest that MoDCs might regulate the immune responses by attracting T cells and CD25+ T cells in the pathogenesis of AD. We also showed the important role of DME on TARC production and the inhibitory effect of the immunosuppressive drugs on TARC production by PBMCs from AD patients, that can regulate ongoing immune responses in the pathogenesis of AD.     

Evaluation of mite allergen-induced Th1 and Th2 cytokine secretion of peripheral blood mononuclear cells from atopic dermatitis patients: association between IL-13 and mite-specific IgE levels

There have been several reports about Th1/Th2 imbalances in atopic dermatitis (AD), but there have been few precise investigations about the differences between Th1 and Th2 cytokine secretion patterns of peripheral blood mononuclear cells (PBMCs) in such patients. We cultured PBMCs, taken from AD patients and healthy subjects, with dust mite extract (DME) and measured subsequent immunoreactive interferon (IFN)-gamma (Th1 cytokine), interleukin (IL)-4, IL-5, and IL-13 (Th2 cytokines) levels in the supernatants by ELISA assays. There is a difference between IL-4 and IL-13 secretion patterns by DME-stimulated PBMCs in AD subjects; immunoreactive IL-4 levels were detectable maximally within 24-h cultures, while IL-13 levels increased time-dependently within 7-day cultures. IL-13 levels were significantly elevated in AD subjects compared to healthy subjects, while IFN-gamma levels did not significantly differ between the two groups. IL-13 levels were significantly higher in AD patients who had high levels (>100 U/ml) of Dermatophagoides pteronyssinus-specific IgE (Dp-IgE) than in those AD patients who had low levels (<10 U/ml) of Dp-IgE. Tacrolimus (FK-506), at a concentration of 10(-8) M, significantly inhibited DME-induced IL-13 production from PBMCs. These findings suggest that IL-13 produced by Th2 cells are involved in IgE overproduction in AD subjects.     

Decreased IL-10 production by psoriatic peripheral blood mononuclear cells stimulated with streptococcal superantigen

The strong association of acute guttate psoriasis and streptococcal throat infection has suggested a role for streptococcal antigens in the pathogenesis of psoriasis. We have reported that psoriatic peripheral blood mononuclear cells (PBMCs) showed significantly lower responses to cytoplasmic membrane-associated protein (CAP) isolated from group A beta-hemolytic streptococci, a kind of streptococcal superantigen. The objectives were to evaluate the abnormal cytokine production by psoriatic PBMCs to streptococcal superantigen, CAP. We compared the production of four different cytokines, i.e. IL-4, IL-5, IL-10, and IFN-gamma, by PBMCs between psoriatic patients and healthy controls after stimulation with CAP or two different staphylococcal superantigens, staphylococcal enterotoxin A (SEA) or E (SEE). When PBMCs were stimulated with CAP, the production of IL-10 was significantly lower by psoriatic PBMCs than by those from healthy controls, whereas those of IL-4, IL-5, or IFN-gamma were not different between the two groups. Such a significant decrease in IL-10 production by psoriatic PBMCs was not observed when they were stimulated with staphylococcal superantigens. Flow cytometric analysis of intracytoplasmic IL-10 demonstrated defective IL-10 production by psoriatic PBMCs in both CD3+ T cells and CD14+ monocytes. There was a significant positive correlation between IFN-gamma production by PBMCs and the proliferation of Vbeta8+ T cells preferentially stimulated by CAP. These data demonstrating the defective IL-10 production by psoriatic PBMCs stimulated with streptococcal superantigen seem to explain why only psoriatic patients evolve sustained and Th-1 deviated skin lesions after streptococcal upper respiratory infection.     

The effect of substance P on peripheral blood mononuclear cells in patients with atopic dermatitis

BACKGROUND: There is increasing evidence that neuropeptides, especially substance P (SP), may be involved in the pathogenesis of atopic dermatitis (AD). OBJECTIVE: We performed this study to determine more precisely the role of SP in AD. METHODS: We separated peripheral blood mononuclear cells (PBMCs) from AD patients and normal controls, and measured proliferation response and cytokine release after adding SP (10(-11), 10(-10) and 10(-9) M). We also compared substance P receptor expression by semi-quantitative RT-PCR. RESULTS: PBMCs from AD patients proliferated at significantly higher rates (ca. by 30%). Semi-quantitative RT-PCR showed that the level of expression of SP receptor increased in AD patients versus normal controls. IL-4 release from PBMCs was significantly higher in AD patients, while IFN-gamma release from PBMCs was significantly lower in AD patients. Different concentrations of SP did not cause any difference in IL-4 and IFN-gamma secretions. However, TNF-alpha release from PBMCs in AD patients increased significantly at 10(-10) and 10(-9) M of SP compared to SP (-) control. IL-10 release from PBMCs increased significantly in AD patients with 10(-9) M of SP compared to SP (-) control. CONCLUSION: SP might aggravate AD by increasing the production of TNF-alpha and IL-10 rather than by affecting IL-4 and IFN-gamma. This different immune response is considered to be the result of upregulated SP receptor in AD.     

他克莫司及金黄色葡萄球菌肠毒素B对特应性皮炎外周血Th17细胞的影响

【摘要】 目的 探讨Th17细胞在急性期特应性皮炎（AD）患儿外周血单一核细胞（PBMC）中的表达,他克莫司和金黄色葡萄球菌肠毒素B（SEB）对AD患儿外周血Th17细胞的影响。 方法 分离急性期中、重度AD患儿及健康对照儿童PBMC,分别加入佛波酯和离子霉素、他克莫司、金黄色葡萄球菌肠毒素B培养,流式细胞仪检测Th17、Th1、Th2细胞比例,ELISA检测培养上清中IL-17、IFN-γ、IL-4表达,RT-PCR法检测Th17特异性核转录因子RORγt mRNA表达。 结果 佛波酯和离子霉素处理后,AD患儿外周血Th17、Th2细胞比例及相关细胞因子IL-17、IL-4水平明显高于健康对照组（P < 0.01）。Th1细胞比例及IFN-γ水平低于健康对照组（P < 0.01）,ROR γt mRNA高于健康对照组（P < 0.01）。他克莫司处理后,AD组和对照组IL-17、IFN-γ、IL-4及ROR γt mRNA水平均显著降低（P < 0.01）。SEB处理后,AD组 Th17细胞比例,IL-17和 RORγt mRNA水平显著高于对照组（P < 0.01）,Th1细胞比例及IFN-γ水平低于对照组（P < 0.01）,Th2细胞比例及IL-4水平高于对照组（P < 0.01）。 结论 他克莫司对AD患儿和健康对照PBMC分泌IL-17、IFN-γ、IL-4均有明显的抑制作用。SEB增强AD患儿外周血Th17细胞表达。     

Effect of an antiallergic drug (Olopatadine hydrochloride) on TARC/CCL17 and MDC/CCL22 production by PBMCs from patients with atopic dermatitis

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by the predominant infiltration of Th2-type cells in lesional skin. Thymus and activation-regulated chemokine (TARC/CCL17) and monocyte-derived chemokine (MDC/CCL22) are Th2-type cytokines, and it has been reported that serum CCL17 and CCL22 levels are associated with AD disease activity. Olopatadine hydrochloride (Olopatadine) is an antiallergic drug with selective histamine H(1) receptor antagonist activity. The effect of Olopatadine on chemokine production by peripheral blood mononuclear cells (PBMCs) in AD patients has not been completely elucidated. OBJECTIVES: This study was undertaken to clarify the effects of Olopatadine on CCL17 and CCL22 production by PBMCs from patients with AD during the treatment. METHODS: We measured plasma levels of CCL17, CCL22, IFNgamma, IL-12 and IL-18 in 15 patients with AD before and after treatment with oral Olopatadine (10 mg/day) for 4 weeks. We also examined disease activity using SCORAD index, eosinophil numbers in peripheral blood and serum levels of LDH. PBMCs from the patients were taken before and after the treatment and cultured with or without dust mite allergen extract (DME) for 3 or 5 days. CCL17, CCL22, IFNgamma, IL-12 and IL-18 levels in the supernatants of cultured PBMCs were measured. RESULTS: SCORAD index and eosinophil numbers in peripheral blood significantly decreased during treatment of AD patients with oral Olopatadine and topical corticosteroids for 4 weeks. The plasma levels of CCL17 and CCL22 significantly decreased after the treatment compared with before the treatment (p<0.05) and were significantly correlated with SCORAD index. PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, showed significantly lower levels of CCL17 production than those taken before the treatment (p=0.018). PBMCs from AD patients taken after the treatment and cultured with DME for 5 days, also showed significantly lower levels of IFNgamma production than those taken before the treatment (p=0.012). CONCLUSION: Our data demonstrate that Olopatadine inhibits CCL17 and CCL22 production by PBMCs from AD patients, which are important regulators of Th2 recruitment in the skin.     

IL-10 augments the IFN-gamma and TNF-alpha induced TARC production in HaCaT cells: a possible mechanism in the inflammatory reaction of atopic dermatitis

The CC-chemokine TARC is known to be a ligand for the CCR4 receptor which in turn is known to be expressed selectively on the Th(2)-subset of lymphocytes. Atopic dermatitis is generally believed to be a Th(2)-type disease, and TARC has been shown to be expressed in the skin lesions of a murine model of AD. IL-10 is an interleukine generally known for its ability to inhibit cytokine production, however it has been found to be highly expressed in the skin from AD patients. We show in this report that IL-10 is able to augment the TARC inducing effects of TNFalpha and IFNgamma in HaCaT cells, a property that may be important in the determination of the composition of the cells of the inflammation in the skin of AD patients. In addition, we show that the IL10 agonist IT 9302, a nona-peptide from the carboxylic end of IL-10, has the same effect on TARC production from HaCaT cells.     

The effects of vitamin K1 and vitamin K2 on the proliferation,cytokine production and regulatory T‐cell frequency in peripheral blood mononuclear cells of paediatric atopic dermatitis patients

We estimated the pharmacological efficacy of vitamin K₁ (VK₁) and VK₂ on the mitogen‐activated peripheral blood mononuclear cells (PBMCs) of paediatric atopic dermatitis (AD) patients. VK₂ suppressed the in vitro proliferation of T‐cell mitogen‐activated PBMCs of AD patients. In contrast, VK₁ had little effect on the PBMC proliferation. The IL‐2 production from the activated PBMCs of AD patients significantly increased (P < .05), while the production significantly decreased by 100 μmol L^?1 VK₂ (P < .01). In addition, 100 μmol L^?1 VK₂ reduced the percentage of CD4+ and CD4+CD25+ cells in PBMCs. These results suggest that VK2 can modulate T‐cell function in PBMCs of AD patients.     

IL-33 and ST2 in atopic dermatitis: expression profiles and modulation by triggering factors

In the acute phase of atopic dermatitis (AD), T-helper type 2 (Th2) cytokines characterize the inflammatory response in the skin. IL-33 is a new tissue-derived cytokine, which is mainly expressed by cells of barrier tissues, and is known to activate Th2 lymphocytes, mast cells, and eosinophils. IL-33 signals through a receptor complex consisting of IL-33-specific receptor ST2 and a co-receptor IL-1RAcP. As IL-33 is known to promote Th2-type immunity, we examined expression profiles of IL-33 and its receptor components in human AD skin, in the murine model of AD, and in various cell models. We found increased expression of IL-33 and ST2 in AD skin after allergen or staphylococcal enterotoxin B (SEB) exposure, as well as in the skin of 22-week-old filaggrin-deficient mice. In addition, skin fibroblasts, HaCaT keratinocytes, primary macrophages, and HUVEC endothelial cells efficiently produced IL-33 in response to the combined stimulation of tumor necrosis factor-α and IFN-γ, which was further enhanced by a mimetic of double-stranded RNA. Finally, the increased expression of IL-33 and ST2 caused by irritant, allergen, or SEB challenge was suppressed by topical tacrolimus treatment. These results suggest an important role for IL-33-ST2 interaction in AD and highlight the fact that bacterial and viral infections may increase the production of IL-33.     

Abnormal expression of interleukin-23 in mycosis fungoides/Sézary syndrome lesions

Progression of mycosis fungoides (MF) to Sézary syndrome (SS) is accompanied by a shift from a T_H1 to a T_H2 cytokine profile. Interleukin (IL)-23 is a novel cytokine that shares a common p40 subunit with the T_H1 inducer, IL-12. IL-23 induces a third profile, T_HIL-17, that is dominant in inflammation and autoimmunity. Although IL-23 induces an eczematous-like skin reaction in mice, and is expressed in T_H1-mediated skin disorders such as psoriasis, it has not been evaluated in MF/SS. To study the role of IL-23 in MF/SS development, 40 MF/SS lesions of all stages were immunohistochemically analyzed with a novel anti-human IL-23 antibody raised against full-length human IL-23. IL-23 was detected with the catalyzed signal amplification system. The intensity and frequency of IL-23 staining were semi-quantitatively graded in both the dermal infiltrate and the epidermis. Increased expression of IL-23 was observed throughout the epidermal keratinocytes and in dermal lymphocytes compared to normal skin. IL-23 intensity did not differ significantly among the stages of MF/SS; however, in stage IVB patients, we observed lower frequency of IL-23 expression in dermal lymphocytes than in other stage patients [P = 0.13, analysis of variance (ANOVA)]. Interestingly, clusters of atypical lymphocytes, especially the epidermotropic tumor cells, demonstrated weak or absent IL-23 staining in 18 of 40 (45%) lesions. This finding was present in 4 of 5 (80%) of the stage IVB lesions and 7 of 11 (64%) of the lesions from Sézary patients. These findings indicate that abnormal IL-23 expression may play a role in the pathogenesis and progression of MF/SS.     

Dehydroepiandrosterone may be one of the regulators of cytokine production in atopic dermatitis

Previous studies in mice have shown that dehydroepiandrosterone (DHEA) increases the production of Th1-associated lymphokines, and of interleukin-2 (IL-2) and interferon-gamma (IFN-γ), by lymphocytes. However, there are no reports concerning the effect of DHEA on the production of Th2-associated lymphokines, IL-4 and IL-5, by lymphocytes in humans. We examined serum DHEA levels in patients with atopic dermatitis (AD), which is thought to be associated with a higher activity of Th2 cells than of Th1 cells. We also studied the effects of DHEA on the production of IL-4 and IL-5 by human lymphocytes. Serum DHEA concentrations in 47 adult male patients with AD aged 19–30 years were significantly lower than those of 53 age-matched healthy male controls. Preincubation of peripheral blood mononuclear cells (PBMCs) with DHEA reduced the IL-4 production by concanavalin A-stimulated PBMCs. Their IL-5 production also showed a tendency to decrease. These results suggest that DHEA may be one of the regulators of IgE synthesis and eosinophil proliferation in patients with AD and it may act by controlling IL-4, IL-5 and IL-2 production by lymphocytes. Received: 12 November 1996