Epicutaneous sensitization with superantigen induces allergic skin inflammation

BACKGROUND: Atopic dermatitis (AD) is characterized by skin infiltration with eosinophils and lymphocytes and expression of Th2 cytokines in acute skin lesions. The skin of patients with AD is frequently colonized with enterotoxin-secreting strains of Staphylococcus aureus. Staphylococcal enterotoxins have been implicated in the exacerbations of the inflammatory skin lesions in patients with AD. OBJECTIVE: We sought to determine whether epicutaneous (EC) sensitization of mice with staphylococcal enterotoxin B (SEB) results in allergic skin inflammation. METHODS: BALB/c mice were EC-sensitized with SEB. Their skin was examined for allergic inflammation and cytokine expression, and their splenocytes were examined for cytokine secretion in response to SEB. RESULTS: EC sensitization with SEB elicited a local, cutaneous, inflammatory response characterized by dermal infiltration with eosinophils and mononuclear cells and increased mRNA expression of the Th2 cytokine IL-4 but not of the Th1 cytokine IFN-gamma. EC-sensitized mice mounted a systemic Th2 response to SEB evidenced by elevated total and SEB-specific IgG1 and IgE. Although EC sensitization with SEB resulted in selective depletion of SEB-specific T-cell receptor Vbeta8+ cells from the spleen and sensitized skin, splenocytes from SEB-sensitized mice secreted relatively more IL-4 and less IFN-gamma than did saline-sensitized controls, consistent with Th2 skewing of the systemic immune response to the superantigen. CONCLUSION: These results suggest that EC exposure to superantigens skews the immune response toward Th2 cells, leading to allergic skin inflammation and increased IgE synthesis that are characteristic of AD.     

"Bystander" amplification of PBMC cytokine responses to seasonal allergen in polysensitized atopic children

BACKGROUND: Atopic children show increased expression and production of the Th2-associated cytokines IL-4, IL-5, IL-13, and IL-9 from PBMCs after stimulation with allergen, but it has previously not been clearly determined whether the Th2-cytokine production is restricted to the inhalant allergen the child is sensitized to, and whether perennial or seasonal allergens induce different cytokine responses. Our purpose was to determine whether in vitro Th2 cytokine production is specific to the sensitizing allergen, and to compare the cytokine responses to a perennial and a seasonal allergen in monosensitized and polysensitized children. METHODS: Using semiquantitative RT-PCR, we analyzed the expression of the cytokines IL-4, IL-5, IL-13, IL-9, IL-10, and IFN-gamma after stimulation of PBMCs with house-dust-mite (HDM) or ryegrass allergen. The cells were sampled from groups of 6-year-old children sensitized to either HDM (n=20) or ryegrass (n=24), or to both allergens (n=20), as well as from a nonatopic group (n=20). RESULTS: After stimulation with HDM allergen, PBMCs from children sensitized only to HDM expressed increased mRNA levels of the Th2 cytokines, but not of IL-10 and IFN-gamma, whereas ryegrass stimulation did not result in increased cytokine expression. PBMCs from children sensitized to HDM and ryegrass expressed increased Th2 cytokines after stimulation with either of the two allergens. In contrast, PBMCs from children sensitized only to ryegrass did not express increased levels after stimulation with either of the allergens. CONCLUSIONS: The expression of Th2 cytokines after in vitro stimulation of PBMCs from atopic children is specific to the sensitizing allergen, indicating that atopic status per se does not affect the type of T-cell response. In addition, T cells specific to seasonal allergens circulate in the blood out of season only if the child is concomitantly sensitized to a perennial allergen.     

Impaired TLR-2 expression and TLR-2-mediated cytokine secretion in macrophages from patients with atopic dermatitis

Background:  In many patients with atopic dermatitis (AD), the disease is complicated by their enhanced susceptibility to bacterial skin infections, especially with Staphylococcus aureus . The pattern recognition receptor toll-like receptor (TLR)-2 recognizes components of S. aureus , for example, lipoteichoic acid (LTA) and peptidoglycan (PGN) and, therefore, might be crucial in the pathogenesis and flare-ups of AD.
Objective:  To investigate TLR-2 expression and cytokine secretion in macrophages from patients with AD compared to healthy controls upon TLR-2 stimulation with PGN, LTA and Pam3Cys.
Methods:  Macrophages were cultivated from highly purified peripheral blood monocytes of AD patients and nonatopic healthy controls and stimulated with PGN, LTA and Pam3Cys in a time and dose–dependent manner. Afterwards, TLR-2 expression and cytokine secretion were measured on protein and mRNA level. TLR-1 and TLR-6 expression were investigated on the mRNA level. Immunohistochemical stainings from punch biopsies were performed to investigate TLR-2 expression in skin macrophages .
Results:  We could clearly show that macrophages from patients with AD expressed significantly less TLR-2, whereas the expression pattern of TLR-1 and TLR-6 were not altered. Macrophages had a reduced capacity to produce pro-inflammatory cytokines such as IL-6, IL-8 and IL-1β after stimulation with TLR-2 ligands.
Conclusion:  Our findings clearly show an impaired TLR-2 expression and functional differences of TLR-2-mediated effects on macrophages of AD patients compared to healthy controls which might contribute to the enhanced susceptibility to skin infections with S. aureus in AD.     

Quantitation of ovine cytokine mRNA by real-time RT-PCR

In this study we describe for the first time the dynamics of the expression of the cytokines, IL-1beta, IL-12p40, TNFalpha in ovine dendritic cells and macrophages after LPS stimulation. Real time RT-PCR was used for the quantitation of these cytokines and IL-4 and IFNgamma as well as two potential housekeeping genes (HKG), ATPase and GAPDH, in mRNAs from ovine leucocyte populations. Both dual-labelled probes (TAMRA/FAM) and SYBR Green assays were utilised, using a Corbett Research RotorGene and ABI 7700 machine. In order to quantitate each cytokine in our assays all C(T) values were compared to a standard curve generated using plasmid DNA containing the cytokine of interest. To validate our assays, concanavalin A-stimulated peripheral blood mononuclear cells (PBMCs) and LPS-stimulated monocyte-derived dendritic cells (MoDC) and monocyte-derived macrophages (MDM?) were examined. We found that peak cytokine mRNA expression was between 3 and 6 h for the cytokines examined except for IL-12p40 where peak cytokine release was around 12 h post-stimulation in MDM? and PBMCs. However, in MoDCs, peak IL-12p40 mRNA expression was observed within 3-6 h. We have identified a sensitive and reliable method for the identification of ovine cytokine mRNAs.     

Staphylococcal alpha-toxin is a strong inducer of interleukin-17 in humans

Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus aureus, with one-third of isolates producing alpha-toxin. Moreover, S. aureus colonization is positively correlated with the severity of eczema. Interleukin-17A (IL-17A) has gained attention in diseases associated with chronic skin infections. The aim of this study was to investigate the effects of sublytic alpha-toxin concentrations on IL-17A production. Sublytic alpha-toxin concentrations strongly induced IL-17A in peripheral blood mononuclear cells (PBMCs), isolated CD4(+) T cells, polarized Th17 cells, and Th17 clones from reactive atopy patch test lesions and blood from AD patients. Alpha-toxin induced IL-17A directly in T cells. The effect of alpha-toxin was further amplified by upregulation of IL-1 in monocytes. In conclusion, higher levels of IL-17A secretion induced by alpha-toxin in the skin partially explain how colonization with S. aureus can contribute to chronic skin inflammation.     

肺癌患者外周血单个核细胞Th1/Th2反应状态及黄芪的调节作用

目的:探讨肺癌患者外周血单个核细胞（PBMC）Th1/Th2免疫反应状态,观察中药黄芪（AG）对其作用。方法:采集并分离肺癌患者和健康志愿者的PBMCs,各分为4组:其中1组即刻冻存待测,其余3组分别为不加药对照组、加 10％AG、20％AG组,培养48h,收集细胞。以IL-2、IFN-γ代表Th1型细胞因子,IL-4、IL-6、IL-10代表Th2型细胞因子,用RT-PCR方法检测肺癌患者PBMC中Th1/Th2型细胞因子mRNA的表达。结果:肺癌患者PBMC中,IL-4、IL-6和IL-10表达阳性率显著高于正常对照（P<0.05）,而IL-2无1例表达（0/23）,IFN-γ仅1例表达;经与黄芪培养后（2种浓度）,肺癌患者Th2型因子与未加AG培养组相比,IL-4、IL-6和IL-10的表达率下降（P<0.05）;而IL-2的表达率显著提高（P<0.05）。结论:肺癌患者外周血的免疫细胞呈现Th2型免疫反应优势状态;黄芪对于肺癌宿主PBMCs Th1/Th2的状态有良好的调节作用,可使肺癌患者PBMCs的Th2型优势免疫反应向Th1方向逆转。     

Interleukin-4 and interleukin-10 are involved in host resistance to Staphylococcus aureus infection through regulation of gamma interferon

Our previous study showed that gamma interferon (IFN-gamma), a T-helper 1 (Th1)-type cytokine, plays a detrimental role in Staphylococcus aureus infection in mice. In this study, the role of Th2-type cytokines such as interleukin-4 (IL-4) and IL-10 in S. aureus infection was investigated. IL-10 mRNA was induced in parallel with IFN-gamma in the spleens and kidneys of mice during S. aureus infection, whereas IL-4 mRNA was induced in the spleens but not in the kidneys of these animals. Spleen cells obtained from S. aureus-infected mice produced lower titers of IFN-gamma and higher titers of IL-4 and IL-10 in response to heat-killed S. aureus than did those from uninfected mice. Administration of anti-IL-4 monoclonal antibody (MAb) or anti-IL-10 MAb inhibited the elimination of S. aureus cells from the kidneys of mice. IFN-gamma mRNA expression was enhanced in the spleens of anti-IL-4 MAb- or anti-IL-10 MAb-treated mice and also in the kidneys of anti-IL-4 MAb-treated animals. Next, we evaluated the role of IFN-gamma in S. aureus infection in IFN-gamma(-/-) mice. An increase in survival rates, a decrease in bacterial numbers in the kidneys, and an amelioration of histologic abnormalities in these organs were observed in IFN-gamma(-/-) mice compared with those in IFN-gamma(+/+) mice. Administration of MAb against IL-4 or IL-10 failed to affect bacterial growth in the spleens and kidneys of IFN-gamma(-/-) mice irrespective of the expression of Th2 response. These results suggest that S. aureus infection induced a Th2 response and that IL-4 and IL-10 might play a protective role through the regulation of IFN-gamma in S. aureus infection.     

Inhibitory activity of CX-659S,a novel diaminouracil derivative,against the rebound phenomenon following withdrawal of corticosteroid therapy for chronic contact hypersensitivity responses

BACKGROUND: CX-659S, a newly discovered anti-inflammatory compound, exerts inhibitory effects on chronic contact hypersensitivity responses (CHRs) induced by repeated application with picryl chloride (PC), which is known to mimic many, if not all, events occurring within lesional skin of patients with atopic dermatitis (AD). CX-659S suppresses the expression of mRNA for interleukin (IL)-4 and IL-10 but not that for IFN-gamma, and inhibits serum IgE production in a chronic CHR model. Although topical corticosteroids have been widely utilized in steroid-responsive dermatoses such as AD, their chronic use may be associated with significant side effects. In addition, a rebound phenomenon often occurs after discontinuation of prolonged use of topical corticosteroids, with enhanced production of IgE and Th2 cell cytokines. The purpose of this study was to assess whether CX- 659S inhibits the rebound phenomenon after discontinuation of chronic treatment with prednisolone in a chronic CHR model in mice. METHODS: The efficacy of CX-659S as a sequential therapeutic agent after discontinuation of chronic treatment with prednisolone was tested on PC-treated ears of BALB/c mice with chronic CHR. Effects were quantified by measurements of ear thickness, serum IgE and cytokine mRNA expression. RESULTS: The rebound phenomenon was confirmed after discontinuation of chronic treatment with prednisolone in chronic CHR in mice, i.e. by evidence of flare thickening of the ear, enhanced expression of mRNA for IL-4 and IL-10 and increased serum IgE. Sequentially applied CX-659S suppressed these rebound phenomena with a good cosmetic result. CONCLUSIONS: CX-659S is the first promising compound with inhibitory activity on the rebound phenomenon following withdrawal of corticosteroid therapy without immunosuppression.     

转录因子T-bet/GATA-3比率评价哮喘患者Th1/Th2失衡及CpG ODN干预机制的研究

目的: 探讨哮喘患者PBMCs中转录因子T-bet/GATA-3比率与Th1/Th2细胞失衡的关系及体外CpG干预后T-bet/GATA3比率的变化及其对Th1/Th2细胞平衡的调节作用。方法: 用RT-PCR法测定30例发作期哮喘患者（哮喘组）及20例慢性阻塞性肺病患者（COPD组）及20例正常人（对照组） PBMCs中T-bet mRNA、GATA-3 mRNA及TLR9 mRNA的表达强度，用ELISA法测定血浆IL-4、IL-5、IL-13和IFNγ的表达水平，以观察哮喘患者PBMCs中转录因子T-bet/GATA-3比率与Th1/Th2细胞失衡的关系。将20例发作期哮喘患者的PBMCs分为2部分，一份加入CpG ODN和PHA（CpG组），一份仅加入PHA（对照组），培养48 h后分别收集培养液和细胞，采用RT-PCR法测定细胞中T-bet mRNA、GATA-3 mRNA及TLR9 mRNA的表达强度，ELISA法测定培养液中IL-4、IL-5、IL-13和IFN-γ的表达水平。结果： 哮喘患者PBMCs中T-bet/GATA-3的比率显著低于COPD患者和正常人，IL-4、IL-5、IL-13的水平显著高于COPD患者和正常人，与T-bet/GATA-3的比率呈负相关，而IFN-γ的水平显著降低，与T-bet/GATA-3的比率呈正相关。哮喘组TLR9的表达强度显著弱于COPD患者和正常人。CpG干预组细胞培养液中IL-4、IL-5和IL-13的水平分别显著低于对照组，IFN-γ的水平显著高于对照组。CpG干预组细胞中T-bet mRNA和TLR9 mRNA的表达强度显著强于对照组，GATA-3 mRNA的表达强度显著低于对照组；T-bet/GATA-3的比率显著高于对照组。结论: 哮喘患者T-bet/GATA-3的比率降低，可以作为评价Th1/Th2细胞失衡的精确指标。CpG ODN可以上调T-bet的表达，下调GATA-3的表达，从而上调T-bet/GATA-3的比率，逆转Th1/Th2细胞失衡，是一种很有前景的哮喘治疗手段。     

IL-23/IL-17炎症轴在咪喹莫特诱导的小鼠银屑病样皮肤损害中的作用

 目的：观察IL-23/IL-17炎症轴在咪喹莫特诱导的小鼠银屑病样皮损形成过程中的作用及变化规律。方法：雌性BALB/c小鼠随机分为正常对照组和咪喹莫特组,采用PASI评分观察银屑病样小鼠模型皮损动态变化;光镜观察皮损组织形态学变化;细胞因子抗体芯片技术对比检测两组小鼠血清及皮损组织中细胞因子谱的变化;采用流式细胞小球微阵列术、实时荧光定量PCR和蛋白免疫印迹分析技术对小鼠血清及皮肤组织中细胞因子含量、mRNA和蛋白表达水平进行检测;流式细胞术分析外周血及脾细胞成分。结果：咪喹莫特诱导小鼠产生红斑、鳞屑、增厚等典型的银屑病样皮损,并随着给药时间的延长呈现一个抛物线型的动态变化;经咪喹莫特外用刺激后,小鼠皮肤及血清中IL-23/IL-17轴相关细胞因子、Th1、Th2和Treg类细胞因子含量及表达水平均显著升高。IL-23/IL-17轴细胞因子表达也呈现一个先升高后降低的动态变化过程。咪喹莫特组小鼠外周血及脾细胞中树突状细胞比例显著升高,脾细胞中Th17细胞比例升高,约为正常对照组的3～4倍,Treg细胞比例约为正常对照组的2倍。结论：咪喹莫特诱导小鼠产生的皮损症状、病理学特征及细胞因子改变都与银屑病相似,是进行银屑病研究可行的动物模型,该模型制备后第1～8天可模拟疾病的发展阶段。Th17细胞活化及IL-23/IL-17轴参与了该模型皮损的形成,并呈现一个先升高后降低的动态变化过程。Th1细胞介导的炎症反应也参与了该模型皮损的形成,并且伴随Treg 和Th2类细胞因子的反馈性升高。     

Percutaneous sensitization with allergens through barrier-disrupted skin elicits a Th2-dominant cytokine response

We investigated whether percutaneous sensitization with different allergens through barrier-disrupted skin regulates the balance of Th1/Th2 cytokine expression. When mice were sensitized with the typical hapten picryl chloride (PiCl) by a single topical application to intact skin, there was an up-regulation in the lymph nodes (LN) of mRNA expression for the Th1 cytokines IL-2 or IFN-γ, and for the Th2 cytokine IL-4. In contrast, sensitization with PiCl after barrier disruption of the skin down-regulated the expression of mRNA for IFN-γ in a tape-stripping number-dependent manner without changing the expression of mRNA for IL-4. When mice were sensitized with house dust mite antigens (MA) by a single topical application to barrier-disrupted abdominal skin, there was a tape-stripping number-dependent up-regulation in the LN of mRNA expression for IL-4 but not for IL-2 or IFN-γ. In the LN, mRNA for the IL-4-inducible immunoglobulins IgE and IgG1, but not for the IFN-γ-inducible IgG2a, were up-regulated after sensitization with MA, while all three immunoglobulin mRNA were augmented after PiCl sensitization through intact skin. Antigenic elicitation by a topical application of PiCl in aural skin of mice sensitized through intact skin consistently increased the expression of mRNA for all three cytokines in the challenged skin, whereas elicitation in mice sensitized through barrier-disrupted skin decreased the expression of mRNA for IL-2 and IFN-γ, but not for IL-4. Antigenic elicitation by subcutaneous injection of MA in aural skin consistently increased the expression of mRNA for IL-4, but not for IL-2 or IFN-γ in the challenged skin. Infiltration of eosinophils in the dermis was more prominent following elicitation with MA in mice sensitized through barrier disruption than with PiCl in mice sensitized through intact skin. These findings suggest that the percutaneous entry of environmental allergens through barrier-disrupted skin is strongly associated with the induction of Th2-dominant immunological responses, as is seen in atopic dermatitis.     

Characterization of spontaneous dermatitis in beige rats with IgE hyperproduction

BACKGROUND: Atopic dermatitis (AD) is a common skin disease characterized by chronic recurrent eczematous lesions, but its exact etiology and mechanism are unclear. We found that beige rats (DAbg/bg), a mutant model of Chediak-Higashi syndrome, develop skin lesions characterized by pruritus, excoriation, erosion and alopecia. We describe the beige rat and examine its possible usefulness as an AD model. METHODS: Beige rats of 4, 8, 13, 16, 26 and 52 weeks were used. Histological analysis of the skin was performed. Plasma IgE and cytokines were measured. Th1 and Th2 cytokines and RANTES mRNA expression of skin and lymph nodes were evaluated. Passive cutaneous anaphylaxis (PCA) reactions were examined, and maximization tests were conducted. RESULTS: Skin lesions begin to develop with increases in serum IgE levels and the expression of IL-4 mRNA in the lymph node and skin. Histologically, skin lesions are characterized by acanthosis, ulceration and inflammatory cell infiltration in the dermis. Inflammatory cells consist of CD3+, CD4+, ED1+, ED2+ and I-A+ mononuclear cells, eosinophils, degranulated mast cells and neutrophils accompanying interleukin (IL)-4, interferon (IFN)-gamma and RANTES mRNA expressions of the skin. Inflammatory cells are reduced during chronification with decreased expressions of IL-4, IFN-gamma and RANTES mRNA. In addition, the rats show a high sensitivity to PCA reactions and maximization tests. CONCLUSIONS: Our results show that some of the skin lesions of beige rats are morphologically similar to human AD, being characterized by inflammatory cell composition in the acute phase, and increased IgE and RANTES levels. However, the inflammatory process and cytokine expression pattern are different from those in human AD.     

Local cytokine profiles of patients with cervical intraepithelial and invasive neoplasia

Several studies have suggested that patients with cervical intraepithelial and invasive neoplasia have reduced levels of Th1 cytokines, and increased levels of Th2 cytokines. Thus, the aim of this study was to delineate the immunological profile associated with lesion progression. Biopsies were obtained from 28 patients with low grade cervical intraepithelial lesions (LSILs), 53 patients with high grade cervical intraepithelial lesions (HSILs), 25 patients with invasive cancer (CA), and 20 healthy controls. Levels of IFN-γ, TNF-α, IL-2, IL-4, IL-10, IL-12, TGF-β1 and TGF-β2 were then assayed by RT-PCR and ELISA for each biopsy sample. For LSILs, higher levels of Th1 cytokines were detected, while HSILs were associated with a Th2 cytokine profile. In contrast, CA tissues were associated with the strongest expression of a Treg cytokine profile. In conclusion the most important contribution of these work is identification of the Treg cytokine profile in HPV progression lesions and in combination, these results suggested that tumor progression is dependent on suppression of cellular immunity.     

Reduced dermal infiltration of cytokine-expressing inflammatory cells in atopic dermatitis after short-term topical tacrolimus treatment

BACKGROUND: In several clinical studies, topical calcineurin inhibitors have been shown to be effective in the treatment of atopic dermatitis (AD). They target signaling pathways that control gene expression, particularly the expression of cytokines. OBJECTIVE: We examined the cellular infiltrate in skin lesions of 10 patients with AD and characterized the cytokine pattern expressed by the infiltrating cells before and after short-term topical therapy with tacrolimus 1% ointment. METHODS: Skin biopsies were examined for histologic alterations (hematoxylin and eosin staining), composition of the cellular inflammatory infiltrate (immunofluorescence), and cytokine expression (ribonuclease protection assay, ELISA, immunofluorescence) before as well as 1 and 3 weeks after initiation of tacrolimus therapy. For comparison, biopsies from nonlesional AD and normal skin were analyzed. Systemic immunologic effects were assessed by analyzing peripheral blood leukocytes (immunofluorescence) as well as in vitro stimulated pan-T-cell cytokine production (ELISA). RESULTS: All patients showed a significant improvement of their skin lesions associated with a marked regression of spongiosis, acanthosis, and density of the cellular infiltrate in the dermis. The last was a result of reduced infiltration of T cells, B cells, and eosinophils. In contrast, the numbers of mast cells did not change. Moreover, the expression of the T H 2 cytokines IL-5, IL-10, and IL-13 in CD4 + T cells was reduced after therapy. Interestingly, tacrolimus therapy was also associated with a reduction of CD8 + T cells expressing the T H 1 cytokine IFN-gamma. Furthermore, the numbers of epidermal CD1a + dendritic cells increased after treatment. In the peripheral blood, a decrease of granulocytes (eosinophils and neutrophils) but no changes in the distribution of lymphocyte subpopulations were noticed. CONCLUSION: Topical tacrolimus treatment has anti-inflammatory effects on AD skin as indicated by reduced infiltration of cytokine expressing inflammatory cells. No evidence for drug-induced systemic immunosuppression was obtained.     

Inflammatory cell numbers and cytokine expression in atopic dermatitis after topical pimecrolimus treatment

BACKGROUND: In several clinical trials the topical application of pimecrolimus was shown to be effective in the treatment of atopic dermatitis (AD). By targeting calcineurin-dependent signaling pathways, pimecrolimus controls cytokine gene expression. The purpose of this study was to investigate the effect of pimecrolimus on the inflammatory infiltrate and cytokine expression pattern in AD upon topical therapy. METHODS: From 10 patients with acute AD, skin biopsies as well as immunophenotype and cytokine production of peripheral blood mononuclear cells (PBMC) were examined before and 3 weeks after therapy. RESULTS: The clinical improvement was associated with a marked regression of histopathological features. In particular, the density of the inflammatory infiltrate mostly containing lymphocytes and eosinophils declined. By double immunofluorescent staining, a reduced expression of the T helper (Th) 2 cytokines interleukin (IL)-5, IL-10, and IL-13 in both CD4+ and CD8+ T cells was demonstrated after therapy. Pimecrolimus therapy was also associated with a reduced expression of the Th1 cytokine interferon (IFN)-gamma. Interestingly, the numbers of epidermal CD1a+ dendritic cells increased following treatment. In the peripheral blood, a decrease of lymphocytes and eosinophils was noticed, but the distribution of lymphocyte subpopulations and their capacity of cytokine production did not change. CONCLUSIONS: Topical pimecrolimus exhibits anti-inflammatory effects in AD by reducing the inflammatory cell infiltrate and cytokine expression in the dermis.     

Immunological response to Parthenium hysterophorus in Indian Patients with Parthenium sensitive atopic dermatitis

Parthenium hysterophorus is the leading cause of airborne contact dermatitis, a type IV hypersensitivity reaction in India. Though there are reports of it causing type-I hypersensitivity in atopic individuals in the form of allergic rhinitis and asthma, there is very little information on its role in pathogenesis of atopic dermatitis (AD), another predominately type I hypersensitivity. In the present study, we evaluated the presence of immediate hypersensitivity to P. hysterophorus in patients with AD and evaluated the in vitro immunological response of P. hysterophorus SPT positive AD patients to stimulation with P hysterophorus allergen. In 70 patients (age 15-45 years) with AD and 70 healthy controls, who were patch test negative to P. hysterophorus, immediate hypersensitivity to P hysterophorus was determined by skin prick test (SPT). In SPT positive patients with AD and SPT negative controls, the absolute eosinophil count (AEC), the total serum IgE and Parthenium specific IgE were determined and PBMC proliferation assay to Parthenium pollen using tritiated thymidine incorporation was done. The IL-4, IL-10, IL-2 and IFN-γ from stimulated PBMCs culture supernatant was also quantified using sandwich ELISA in both groups of patients. Twenty-five (35.7%) of 70 patients with AD had a positive SPT to Parthenium, compared to 3 (4.3%) of controls. The mean AEC, the mean total IgE and Parthenium specific IgE were significantly elevated in SPT positive AD patients vis-à-vis SPT negative controls. Similarly in the Parthenium specific PBMCs proliferation assay, the stimulation index as well as the Th2 cytokine (IL-4 and IL-10) profile were significantly elevated in SPT positive AD patients vis-à-vis SPT negative controls but there was no difference in the Th1 cytokine (IL-2 and IFN-γ) profile. Our study suggests that a third of patients with AD demonstrated a type I hypersensitivity to P. hysterophorus with a Th2 biased cytokine profile (IL-4 and IL-10) in culture supernatant of Parthenium stimulated PBMCs in these patients.