Clinical study of acupuncture combined with medication in the treatment of skin pruritus in maintenance hemodialysis patients / 针灸推拿医学（英文版）

Objective:To observe the clinical effect of acupuncture combined with Western medicine in the treatment of skin pruritus in maintenance hemodialysis patients.Methods:Eighty patients were randomly divided into a control group and an observation group,with 40 cases in each group.The control group was given loratadine orally,and the observation group was given acupuncture treatment in addition to the treatment used in the control group.The four-item itch questionnaire(FIIQ)score,indicators for skin barrier function,and serum interleukin(IL)-2 and IL-31 levels were compared.The efficacy was judged after the treatment ended.Results:The total effective rate was higher in the observation group than in the control group(P<0.05).After treatment,the site,frequency,severity of pruritus,sleep impact sub-scores,and FIIQ total score in both groups were reduced compared with those before treatment(P<0.05),and all scores in the observation group were lower than those in the control group(P<0.05).The stratum corneum hydration(SCH)and transepidermal water loss(TEWL)in the V-shaped area of the chest,the flexor side of the forearm,and the extensor side of the lower leg were not significantly changed in the control group(P>0.05);the SCH and TEWL in the V-shaped area of the chest,the flexor side of the forearm,and the extensor side of the lower leg in the observation group were improved(P<0.05),and all were better than those in the control group(P<0.05).The serum IL-2 and IL-31 levels in the control group did not change significantly(P>0.05);the serum IL-2 and IL-31 levels in the observation group were both significantly decreased(P<0.05)and were lower than those in the control group(P<0.05).Conclusion:Acupuncture combined with loratadine is highly effective in the treatment of pruritus in maintenance hemodialysis patients,and it can relieve pruritus,improve skin barrier function,and reduce serum IL-2 and IL-31 levels.

Expression of interleukin-31 in hypertrophic scar from postoperative incision tissue / 中华医学美学美容杂志

Objective:To explore the interleukin-31 protein expression in the hypertrophic scar of incision tissue after surgery and its underlying pathological impact.Methods:From February 2022 to February 2023, three HS patients scar tissue (HS) and their normal skin tissue (Control, NS) were obtained. Two patients were female and one patient was male. The tissues were fixed in 4% formalin and embedded in paraffin. Haematoxylin-eosin (HE) stain and immunohistochemical stain were used to evaluate the epidermal thickness, myofibroblasts of dermis and the expression level of IL-31 between HS and NS.Results:The epidermis thickness was (303.88±46.03) μm in HS group, while (133.02±17.40) μm in NS group ( t=12.60, P<0.001). The expression level of IL-31 protein was measured by IRS score and positive cell density. The IRS score was 9.89±2.03 of the basal layer in HS group and was 4.33±1.66 of the basal layer in NS group. The positive cell density was 786 343.83±159 627.97 of the basal layer in HS group ( P<0.001) and was 555 457.61±128 097.21 of the basal layer in NS group ( P=0.014). In the dermis layer, the IRS score was 7.11±1.05 in HS group and was 4.33±0.71 in NS group, the positive cell density was 156 760.97±26 046.10 in HS group ( P<0.001) and was 49 576.01±52 369.33 in NS group ( P<0.001). In the dermis layer, the count of myofibroblasts was 120.44±15.75 in HS group while was 27.39±14.89 in NS group ( t=23.79, P<0.001). Conclusions:Our study demonstrates that both myofibroblast count and IL-31 protein expression level are notably increased in HS patients. The expression of IL-31 protein is prominent in the cytoplasm of myofibroblasts, basal cells, macrophages and mast cells which could implicate that IL-31 may be a potential therapeutic target to enhance the resolution of HS.

Mechanisms of pruritus in bullous pemphigoid / 中华皮肤科杂志

Pruritus is one of the typical clinical manifestations of bullous pemphigoid (BP) . In recent years, researchers have gradually recognized that the histamine-independent itch pathway plays an important role in BP. Eosinophils, basophils, interleukin (IL) -31, IL-4, IL-13, thymic stromal lymphopoietin, periostin and substance P are all closely related to the occurrence of pruritus in BP. This review mainly elaborates research progress in mechanisms related to pruritus in BP.

Characteristics of Pruritus according to Morphological Phenotype of Psoriasis and Association with Neuropeptides and Interleukin-31

Association Between Epithelial Cytokines and Clinical Phenotypes of Elderly Asthma

PURPOSE: Asthma in the elderly has different clinical features including more severe phenotypes with higher comorbidities. Epithelial cells are known to initiate innate/adaptive immune responses in asthmatic airways. We investigated clinical features and epithelial derived cytokine levels in elderly asthmatics compared to non-elderly asthmatics in a cross-sectional cohort of adult asthmatics in order to further understand its pathogenic mechanisms. METHODS: A total of 1,452 adult asthmatics were enrolled from a single tertiary hospital and were classified into 2 groups: 234 elderly (≥ 60 years at initial diagnosis) and 1,218 non-elderly (< 60 years at initial diagnosis) asthmatics. Asthma-related clinical parameters were compared between the 2 groups. Serum levels of epithelial cell-derived cytokines including interleukin (IL)-31, IL-33, IL-8, eotaxin-2, transforming growth factor beta 1 (TGF-β1) and periostin were measured by enzyme-linked immunosorbent assay. RESULTS: Significantly higher prevalence rates of late-onset asthma (onset age ≥ 40 years) and severe asthma, as well as the lower rate of atopy, blood/sputum eosinophil counts, total immunoglobulin E and eosinophil cationic protein levels were noted in elderly asthmatics compared to non-elderly asthmatics (P < 0.05, respectively). The forced expiratory volume in 1 second (FEV1, % predicted) level tended to be lower in elderly asthmatics (P = 0.07). In addition, serum IL-33 and IL-31 levels were significantly lower in elderly asthmatics, while no differences were found in the serum level of IL-8, eotaxin-2, TGF-β1 or periostin. Among elderly asthmatics, subjects with severe asthma had lower FEV1 (% predicted) value, but showed significantly higher serum levels of eotaxin-2 and TGF-β1, than those with non-severe asthma (P < 0.05 for each). CONCLUSIONS: These findings suggest that age-related changes of epithelial cell-derived cytokines may affect clinical phenotypes and severity of elderly asthma: decreased levels of IL-33 and IL-31 may contribute to less Th2 phenotype, while increased levels of eotaxin-2 and TGF-β1 may contribute to severity.

Relationship of serum vitamin D and interleukin-31 levels to allergic or nonallergic rhinitis in children

PURPOSE: Serum vitamin D (25-hydroxyvitamin D, 25[OH] D) and interleukin-31 (IL-31) are related to atopic dermatitis, but their relationship with allergic rhinitis is unclear. The purpose of this study was to compare the levels of serum IL-31 and 25 (OH) D between the allergic rhinitis (AR), nonallergic rhinitis (NAR), and control groups and to investigate the relationship between IL-31 and 25 (OH) D. METHODS: We recruited 59 children with only rhinitis and 33 controls without any allergic diseases. Serum IL-31 and 25(OH) D levels were assayed using an enzyme-linked immunosorbent assay and high-performance liquid chromatography, respectively. The patients were considered to have atopic sensitization if the levels of serum specific IgE to inhalant allergens as assessed using immunoCAP were ≥0.35 IU/mL or if they tested positive for one or more allergens by the skin prick test. RESULTS: Of children with rhinitis, 25 had nonatopy (NAR), and 34 children had atopy (AR). Serum 25(OH) D levels were significantly lower in the rhinitis group than in the control group, while there was no significant difference serum 25(OH) D levels between the AR and NAR groups. Children with rhinitis demonstrated higher serum IL-31 levels than controls; however, there was no difference in serum IL-31 levels between the AR and NAR groups. Serum 25(OH) D levels were inversely correlated with serum IL-31 levels and blood eosinophil counts. On the other hand, serum 25(OH) D levels were not correlated with total serum IgE levels. CONCLUSION: Serum 25(OH) D and IL-31 may play a role in the pathogenesis of rhinitis via mechanisms other than IgE-related pathway.

Interleukin-31, Interleukin-31RA, and OSMR Expression Levels in Post-burn Hypertrophic Scars

BACKGROUND: Although several studies have shown the role of interleukin-31 (IL-31) and its receptors in inducing pruritus in certain skin disorders, knowledge of its role in post-burn hypertrophic scars is insufficient. Therefore, the histopathological expression levels of IL-31, IL-31 receptor alpha (IL-31RA), and oncostatin M receptor (OSMR) in post-burn hypertrophic scar tissues were investigated and compared with normal tissue expression levels. METHODS: Samples of hypertrophic scar tissue were obtained from 20 burn patients through punch biopsy. Normal samples were obtained from areas adjacent to the burn injury site of the same patients. Samples were placed in 10% neutral buffered formalin, embedded in paraplast, and processed into serial 5-μm sections. Immunohistochemistry results were semi-quantitatively evaluated for IL-31, IL-31RA, and OSMR. By hematoxylin and eosin staining, epidermal and dermal thickness were assessed with a microscope and digital camera. Intensities were rated on a scale of 1 to 4. RESULTS: Percentages for IL-31, IL-31RA, and OSMR in the epidermal basal layer cell cytoplasm were significantly greater in the burn scar tissue compared to normal skin, as well as the dermal and epidermal thickness (p < .05). There was a significant difference in IL-31 epidermal basal layer intensity in burn scar tissue compared to normal skin (p < .05). Besides the OSMR basal layer intensity, IL-31 and IL-31RA intensities between the burn scar and normal tissues were not significant. However, correlations were significant, indicating that the greater the infiltration percentage, the higher the intensity (p < .05). CONCLUSIONS: IL-31, IL-31RA, and OSMR expression levels are increased in hypertrophic scars compared with normal tissue.

Serum interleukin-31 level and pruritus in atopic dermatitis: A Meta-analysis / 中南大学学报(医学版)

Objective:To investigate associations of interleukin-31 (IL-31) and pruritus in atopic dermatitis (AD) with Meta-analysis.Methods:Materials were extracted from the citations listed in the following databases:PubMed,Science Direct,Web of Science and Cochrane.Key search terms included:atopic dermatitis,pruritus,and IL-31.The Meta-analysis was used to analyze the correlation between pruritws in AD and IL-31 expression level.Results:The Meta-analysis showed that serum IL-31 levels were higher in AD patients than those in the healthy controls.The levels of IL-31 were higher in severe AD patients than those in the mild and moderate AD patients.Moreover,a positive correlation between serum IL-31 levels and severity of pruritus was identified.Conclusion:Increased serum levels of IL-31 generally exist in the AD patients,and it may accelerate the pruritus in the AD patients.

The importance of IL-31 in pruritus in patients with atopic dermatitis / Шинэ санаа Шинэ нээлт

Atopic dermatitis is a common, chronic, relapsing, allergic skin disease characterized by stronglypruritic eczematous skin lesions. Pruritus is the hallmark of atopic dermatitis, with a significant impact on quality of life for the patients. Many patients define their disease severity by the intensity of pruritus rather than by the appearance of skin lesions. Although the pruritus is one of the most essential symptoms of atopic dermatitis, its pathophysiology is still unclear. The lack of effect of antihistamines argues against a role of histamine in causing atopic dermatitis–related pruritus. Neuropeptides, proteases, kinins, and cytokines induce itching. In the early stages of atopic dermatitis Th2 cellsplay a significant role. Interleukin-31 is a cytokine produced by T cells that increases the survival ofhematopoietic cells and stimulates the production of inflammatory cytokines by epithelial cells. Our study aim is to investigate the correlation between the serum level of IL-31 and the severity of disease.A total of 80 participants with a diagnosis of atopic dermatitis based on the Hanifin and Rajka criteriaare selected from all patients of the National Dermatology center. A questionnaire consisting of theparticipant’s general information and disease history is obtained. The severity of disease is assessed by using SCORAD (Scoring atopic dermatitis) and patients with AD will be grouped into mild ( 50 points) disease groups. Serum IL-31 is measured using ELISA from peripheral blood.The main symptoms were pruritis (91,3%) and xerosis (78,8%). The serum IL-31 and NGF was higher in severe patients while the pruritus and sleep loss were stronger in those patients. Serum IL-31 was significantly correlated to Scorad index and sleep loss (р<0,05).IL-31 could be itch biomarkers. IL-31 has a role in pathogenesis of pruritus and atopic dermatitis.

Expressions and diagnostic value of interleukin-3 1 in tuberculous pleural effusion / 中华传染病杂志

Objective To analyze the expression of interleukin (IL)-31 in tuberculous pleural effusion,and to evaluate its diagnostic value of tuberculous effusion.Methods Seventy-one patients with pleural effusion were enrolled,including 40 cases of tuberculous pleural effusion and 31 cases of malignant pleural effusion.Luminex method was applied to detect the IL-31 expression in pleural effusion.IL-31 levels were compared using non-parametric Mann-WhitneyU test,and the receiver operator characteristic (ROC)curve was used to elvaluate the diagnostic value of IL-31 .Results IL-31 expression in tuberculous pleural effusion was significantly higher than that in malignant pleural effusion with statistical significance (529.4 ng/L vs 13.8 ng/L,U =62,P <0.01 ).Based on the level of IL-31 expression,area under the ROC curve was 0.95 with the optimum cut-off value of 67.5 ng/L.Thus,the sensitivity and specificity of IL-31 ≥67.5 ng/L for diagnosis of tuberculous pleurisy were 82.5 % (95 %CI :73.3% - 94.2%)and 100.0% (95 %CI :91 .4%-100.0%),respectively.Conclusion IL-31 is highly sensitive and specific for the diagnosis of tuberculous pleural effusion, which favors the differentiation of tuberculosis from malignance.

Relationship between serum 25-hydroxyvitamin D and interleukin-31 levels, and the severity of atopic dermatitis in children / 소아과

PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory relapsing skin disorder. Vitamin D plays a pivotal role in the development of AD, and interleukin (IL) 31 is known to be related to pruritus in AD. The aim of our study was to determine whether 25-hydroxyvitamin D (25(OH)D) levels are related to IL-31 levels or to the severity of AD. METHODS: We enrolled 91 children with AD and 32 control subjects without history or symptoms of allergic diseases. Blood was drawn to evaluate complete blood cell count, total eosinophil count (TEC), and total IgE, specific IgE to common allergens, 25(OH)D, and IL-31 levels. Serum 25(OH)D and IL-31 levels were measured using high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. The scoring atopic dermatitis (SCORAD) index was used to evaluate the severity of AD. RESULTS: The mean 25(OH)D level was significantly lower in the AD group than in the control group; 25(OH)D decreased greatly in the moderate and severe AD groups compared with the mild AD group. Children with atopic sensitization showed significantly lower 25(OH)D levels than nonatopic children. However, serum IL-31 levels were not related to AD group, SCORAD index, or 25(OH)D levels. The SCORAD index was inversely correlated with serum 25(OH)D level and positively correlated with TECs and total IgE levels. Children with moderate and severe AD had significantly higher TECs than children with mild AD. CONCLUSION: Vitamin D is related to the severity of AD independently of IL-31.

Relationship between serum interleukin-31/25-hydroxyvitamin D levels and the severity of atopic dermatitis in children

PURPOSE: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disease. Vitamin D and interleukin-31 (IL-31) are known to be related to the pathogenesis of AD with pruritus. The purpose of this study was to investigate the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) and IL-31 and the disease severity of AD in children with AD. METHODS: We recruited 160 children with AD and 42 controls. We used the SCORing Atopic Dermatitis (SCORAD) index to measure the severity of AD. Serum IL-31 and 25(OH)D levels were assayed using enzyme-linked immunosorbent assay and high-performance liquid chromatography, respectively. Serum levels of total IgE, specific IgE to common allergens and peripheral blood total eosinophil count were carried out in children with AD. RESULTS: Serum IL-31 level was significantly higher in AD group compared to control group and 25(OH)D level was significantly lower in AD group than control group. Serum IL-31 level showed the highest level in severe AD group followed by moderate and mild AD group, whilst serum 25(OH)D level was the lowest in severe AD group compared to moderate and mild AD group. There was no difference in serum IL-31 level between AD group and nonatopic dermatitis group. IL-31 level was positively correlated with subjective SCORAD index indicating pruritus in children with AD, and 25(OH)D was inversely correlated with SCORAD index. CONCLUSION: IL-31 and vitamin D may be related to the pathogenesis of AD, especially with regard to the pruritus.

Blood Level of IL-31, Stem Cell Factor, and B Cell-Activating Factor in Persistent Allergic Rhinitis Patients

BACKGROUND AND OBJECTIVES: Stem cell factor (SCF), B cell-activating factor (BAFF) and Interleukin (IL)-31 are related to allergic diseases such as atopic dermatitis or asthma. But they have not been sufficiently investigated in connection with IgEmediated allergic rhinitis. In this study, we evaluated the association between plasma concentrations of these cytokines and allergic rhinitis. SUBJECTS AND METHODS: A comparative study of the concentrations of plasma SCF, BAFF and IL-31 were conducted between persistent allergic rhinitis patients and a healthy control group using ELISA. RESULTS: Plasma BAFF and IL-31 concentrations were significantly increased in allergic rhinitis group (BAFF, 1,255 pg/mL, Plasma BAFF and IL-31 concentrations were significantly increased in the allergic rhinitis group (BAFF, 1,255 pg/mL, p<0.001;IL-31, 221 pg/mL, p<0.001) than in the control group (BAFF, 1,089 pg/mL;IL-31, 153 pg/mL). But the level of SCF did not exhibit any difference between the allergic rhinitis patients and the control group. CONCLUSION: Our results suggest that plasma BAFF and IL-31 might be associated with the inflammatory mechanism of persistent allergic rhinitis patients.

Correlation between interleukin-31 expression on peripheral blood mononuclear cells and disease severity of pediatric patients with atopic dermatitis / 中华皮肤科杂志

Objective To evaluate the significance of human interleukin-31(IL-31)in the pathogenesis of atopic dermatitis and its correlation with pruritus in patients with atopic dermatitis(AD).Methods Twenty-two children with mild to severe atopic dermatitis and 22 age-matched healthy controls were included in this study.Patients and controls were randomly and equally assigned into stimulation and non-stimulation groups.Venous blood samples were obtained from all participants,peripheral blood mononuclear cells were isolated from these samples and cultured with(stimulation groups)or without(non-stimulation groups)staphylococcal enterotoxin B(SEB)for 24 hours.Then,the mRNA expression of IL-31 on PBMCs was assessed via real-time reverse transcription-PCR.ELISA was used to detect the total serum IgE level in these objects.The severity of AD in patients was rated according to scoring atopic dermatitis(SCORAD).The relationship between the mRNA expression of IL-31 and the level of serum total IgE.severity of atopic dermatitis,and degree of pruritus.was evaluated.Results The expression of IL-31 mRNA on non-stimulated PBMCs from patients was 23.2 folds as high as that from the healthy controls(P＜0.01).The stimulation with SEB upregulated the mRNA expression of IL-31 on PBMCs.and the increase on PBMCs from patients was 20.44 times of that from the controls.The total serum IgE level was 260.05 IU/mL(5.9-1131.01 IU/mL)and 17.7 IU/mL(5-140.7 IU/mL)in the Patients and controls respectively(P＜0.01).There was no significant correlation between the mRNA expression of IL-31 and disease severity or total serum IgE level(r=0.07.0.22respectively.both P＞0.05)in patients witll AD.Condusions IL.3 1 is involved in t11e pathogenesis of AD,which is unlikely to be IgE-dependent.SEB can induce the rapid expression of IL-31 on PBMCs of healthy human,and is an important modulator for the production of IL-31.

Association between Interleukin 31 Receptor A Gene Polymorphism and Schizophrenia in Korean Population

Recently, Sun et al (2008) reported that the IL6R polymorphism is associated with schizophrenia. Therefore, to detect the association between polymorphisms of interleukin 31 receptor A (IL31RA) and schizophrenia, we genotyped 9 SNPs [rs9292101 (intron 1), rs1009639 (exon 2, Pro43Pro), rs2161582 (intron 2), rs68761890 (intron 5), rs16884629 (intron 6), rs11956465 (intron 12), rs12153724 (intron 12), and rs16884641 (intron 14)] using the Golden Gate assay on Illumina BeadStation 500 GX. Two hundred eighteen patients with schizophrenia and 379 normal subjects were recruited. Patients with schizophrenia were diagnosed according to DSM-IV, and control subjects without history of psychiatric disorders were selected. We used SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs for the evaluation of genetic data. Of nine polymorphisms, three SNPs (rs9292101, rs1009639, and rs11956465) were associated with schizophrenia. The rs9292101 and rs11956465 showed significant associations with the risk of schizophrenia in the codominant [rs9292101, odds ratio (OR)=0.74, 95% confidence interval (CI)=0.58~0.95, p=0.017] and recessive (rs11956465, OR=0.64, 95% CI=0.42~0.96, p=0.034) models, respectively. The rs1009639 also was statistically related to schizophrenia in both codominant (OR=0.76, 95% CI=0.60~0.97, p=0.025) and dominant (OR=0.66, 95% CI=0.44~0.98, p=0.035) models. Two linkage disequilibrium (LD) blocks were made. In the analysis of haplotypes, a haplotype (GCT) in block 1 and a haplotype (CCACAG) in block 2 showed significant associations between schizophrenia and control groups (haplotype GCT, frequency=0.509, chi square=4.199, p=0.040; haplotype CCACAG, frequency=0.289, chi square=5.691, p=0.017). The results suggest that IL31RA may be associated with risk of schizophrenia in Korean population.