scholarly journals The Role of Serum Th1, Th2, and Th17 Cytokines in Patients with Alopecia Areata: Clinical Implications

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3397
Author(s):  
Anna Waśkiel-Burnat ◽  
Marta Osińska ◽  
Anna Salińska ◽  
Leszek Blicharz ◽  
Mohamad Goldust ◽  
...  

Alopecia areata is a type of non-scarring hair loss. The dysregulation of numerous systemic Th1 (IL-2, IFN-γ, TNF, IL-12, and IL-18), Th2 (IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17E, IL-31 and IL-33) and Th17 (IL-17, IL-17F, IL-21, IL-22, IL-23 and TGF-β) cytokines was observed in patients with alopecia areata. Positive correlations between the severity of alopecia areata and an increased serum level of various cytokines including IL-2, TNF, IL-12, IL-17, and IL-17E were reported in the literature. An increased serum level of numerous cytokines, such as IL-2, IL-6, TNF, IL-12, IL-17E, and IL-22, was described as positively correlated with the duration of the disease. Moreover, it was shown that increased pre-treatment serum level of IL-12 was a positive, while increased serum levels of IL-4 and IL-13 were negative prognostic markers for the efficacy of diphenylcyclopropenone. In conclusion, alopecia areata is associated with the dysregulation of systemic Th1, Th2 and Th17 cytokines with their role in the pathogenesis, clinical manifestations and prognosis of the disease. Available data indicate the most significant role of serum IL-2, TNF, IL-12, IL-17, and IL-17E as markers of disease activity. The serum levels IL-4, IL-12 and IL-13 may be useful as potential predictors of diphenylcyclopropenone efficacy.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 47.2-47
Author(s):  
C. Gioia ◽  
B. Lucchino ◽  
C. Iannuccelli ◽  
G. Dolcini ◽  
M. DI Franco

Background:Fibromyalgia (FM) is a common rheumatic disease characterized by chronic widespread pain, sleep and mood disorders. A higher prevalence of FM in women compared with men is well known, although the specific differences in clinical manifestations related to gender are still poorly defined. Brain-Derived Neurotrophic Factor (BDNF) is an endogenous growth factor that gained attention for its potential as biomarker of several diseases, including FM and depression.Objectives:The aims of this study were to investigate gender-related difference among males and females affected by FM in clinical manifestations, depressive features and BDNF serum level, evaluating also the diagnostic potential of the latter.Methods:We consecutively enrolled adult patients affected by FM (ACR 2016) referring to our out-patient clinic. Each subject underwent clinical and answered to questionnaires for the severity of FM symptoms (Revised Fibromyalgia Impact Questionnaire, R-FIQ) and depressive symptoms (Beck Depression Inventory-II, BDI-II). We collected blood samples from a subgroup of patients of both sexes, matched for age, for BDNF serum level dosage through ELISA. BDNF levels were assessed also in a control group, matched for sex and age.Results:The cohort was composed by 201 FM patients (172 F, 29 M), mean age 49.13. Females showed higher values of R-FIQ total score (p=0,0005) as well the specific items of the R-FIQ for pain (p=0,013), fatigue (p=0,014), memory problems (p=0,007), tenderness to touch (p<0,0001), balance problems (p<0,0001) and sensitivity to environmental stimuli (p=0,012) when compared with males (fig. 1). There was no difference in BDI-II between males and females, but notably male patients reported a significantly higher frequency of coexisting depressive disorder (p=0,038) (fig. 2). Serum BDNF levels were evaluated in 40 FM patients and 40 healthy controls (HC) (F:M 1:1). BDNF levels were significantly lower in FM patients compared with HC (p<0,0001). Among FM patients, BDNF levels were lower in males compared with females (p<0,0001) (fig.3). BDNF did not correlate with any clinical and clinimetric parameter. BDNF showed a good diagnostic performance (AUC=0,89, CI95%=0,82-0,9630, p<0,0001) (fig. 4). At a cut-off value <6,47 ng/dl, BDNF showed a specificity of 75% and a sensibility of 92,31%,(CI 95%=79,68-97.35) for FM identification (LR=3,692).Conclusion:FM clinical manifestations are strongly dependant from gender. While females present a more severe disease and a higher burden of symptoms, mood disorders tend to be a major characteristic of males with FM. Reduced BDNF serum levels have been reported as typical of depressive disorders. Our findings of lower BDNF levels in male FM patients compared to females support this hypothesis. BDNF have potential as biomarker of the disease and should be validated in larger cohorts.References:[1]Sarzi-Puttini et al. Nature Reviews 2020[2]Colucci-D’Amato et al. Int J Molecular Sciences 2020[3]Nugraha et al. Rheumatol Int 2012[4]Schmitt et al. Ann Med 2016[5]Melchior et al. Neuroscience 2016[6]Stefani et al. Neuroscience Letters 2012Disclosure of Interests:None declared


2020 ◽  
Vol 34 ◽  
pp. 205873842092944
Author(s):  
Chieh-Shan Wu ◽  
Shih-Chao Lin ◽  
Shiming Li ◽  
Yu-Chih Chiang ◽  
Nicole Bracci ◽  
...  

Atopic dermatitis (AD) is a chronic inflammatory disease of the skin that substantially affects a patient’s quality of life. While steroids are the most common therapy used to temporally alleviate the symptoms of AD, effective and nontoxic alternatives are urgently needed. In this study, we utilized a natural, plant-derived phenolic compound, phloretin, to treat allergic contact dermatitis (ACD) on the dorsal skin of mice. In addition, the effectiveness of phloretin was evaluated using a mouse model of ACD triggered by 2,4-dinitrochlorobenzene (DNCB). In our experimental setting, phloretin was orally administered to BALB/c mice for 21 consecutive days, and then, the lesions were examined histologically. Our data revealed that phloretin reduced the process of epidermal thickening and decreased the infiltration of mast cells into the lesion regions, subsequently reducing the levels of histamine and the pro-inflammatory cytokines interleukin (IL)-6, IL-4, thymic stromal lymphopoietin (TSLP), interferon-γ (IFN-γ) and IL-17A in the serum. These changes were associated with lower serum levels after phloretin treatment. In addition, we observed that the mitogen-activated protein kinase (MAPK) and NF-κB pathways in the dermal tissues of the phloretin-treated rodents were suppressed compared to those in the AD-like skin regions. Furthermore, phloretin appeared to limit the overproliferation of splenocytes in response to DNCB stimulation, reducing the number of IFN-γ-, IL-4-, and IL-17A-producing CD4+ T cells in the spleen back to their normal ranges. Taken together, we discovered a new therapeutic role of phloretin using a mouse model of DNCB-induced ACD, as shown by the alleviated AD-like symptoms and the reversed immunopathological effects. Therefore, we believe that phloretin has the potential to be utilized as an alternative therapeutic agent for treating AD.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Dorota Diakowska ◽  
Krystyna Markocka-Mączka ◽  
Piotr Szelachowski ◽  
Krzysztof Grabowski

The aim of the study was the investigation of relationship between cachexia syndrome and serum resistin, adiponectin, and apelin in patients with gastroesophageal cancer (GEC).Material and Methods. Adipocytokines concentrations were measured in sera of 85 GEC patients and 60 healthy controls. They were also evaluated in tumor tissue and appropriate normal mucosa of 38 operated cancer patients.Results. Resistin and apelin concentrations were significantly higher in GEC patients than in the controls. The highest resistin levels were found in cachectic patients and in patients with distant metastasis. Serum adiponectin significantly decreased in GEC patients with regional and distant metastasis. Serum apelin was significantly higher in cachectic patients than in the controls. Apelin was positively correlated with hsCRP level. Resistin and apelin levels increased significantly in tumor tissues. Weak positive correlations between adipocytokines levels in serum and in tumor tissue were observed.Conclusions. Resistin is associated with cachexia and metastasis processes of GEC. Reduction of serum adiponectin reflects adipose tissue wasting in relation to GEC progression. Correlation of apelin with hsCRP can reflect a presumable role of apelin in systemic inflammatory response in esophageal and gastric cancer.


2020 ◽  
Vol 66 (1) ◽  
pp. 25-32
Author(s):  
Elena Kostova ◽  
Slavica Shubeska Stratrova

The aim of this study was to analyze TIMP-1 and TIMP-2 serum levels in patients with colorectal cancer (CRC) and to correlate the results with the pathological stage of the disease and outcome in order to evaluate the role of TIMP-1 and TIMP-2 serum levels as prognostic markers. The investigation has been made on 82 patients with operable CRC without distant metastases, who had undergone blood tests in order to determine the TIMP-1 and TIMP-2 serum levels in the following points of time: preoperatively, as well as 3, 6, 9 and 12 months postoperatively. Significant differences were found between serum levels of TIMP-1 and TIMP-2 obtained preoperatively and postoperatively, as well as significant association of serum TIMP-1 levels obtained preoperatively in CRC patients in stage I and III, in the 3th and in the 6th month (p<0.001) postoperatively as defined points of time with the outcome of CRC patients. Serum TIMP-2 levels obtained preoperatively was significantly associated with the outcome of the CRC patients. Analysis of the obtained TIMP-1 and TIMP-2 serum levels in CRC patients showed statistically significant differences with: disease progression, occurrence of liver metastasis, prior to and post chemotherapy treatment. The results derived a conclusion that the serum levels of TIMP-1 and TIMP-2 could be indicators for occurrence and progression of CRC, as well as valuable and useful markers for following the effects of chemotherapy treatment. Keywords: colorectal cancer, TIMP-1, TIMP-2, prognosis


Pathogens ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 57
Author(s):  
Momen Askoura ◽  
Hisham A. Abbas ◽  
Hadeel AlSadoun ◽  
Wesam H. Abdulaal ◽  
Amr S. Abu Lila ◽  
...  

Hepatitis C virus (HCV) is one of the most epidemic viral infections in the world. Three-quarters of individuals infected with HCV become chronic. As a consequence of persistent inflammation, a considerable percentage of chronic patients progress to liver fibrosis, cirrhosis, and finally hepatocellular carcinoma. Cytokines, which are particularly produced from T-helper cells, play a crucial role in immune protection against HCV and the progression of the disease as well. In this study, the role of interleukins IL-33, IL-17, and IL-25 in HCV patients and progression of disease from chronicity to hepatocellular carcinoma will be characterized in order to use them as biomarkers of disease progression. The serum levels of the tested interleukins were measured in patients suffering from chronic hepatitis C (CHC), hepatocellular carcinoma (HCC), and healthy controls (C), and their levels were correlated to the degree of liver fibrosis, liver fibrosis markers and viral load. In contrast to the IL-25 serum level, which increased in patients suffering from HCC only, the serum levels of both IL-33 and IL-17 increased significantly in those patients suffering from CHC and HCC. In addition, IL-33 serum level was found to increase by liver fibrosis progression and viral load, in contrast to both IL-17 and IL-25. Current results indicate a significant role of IL-33 in liver inflammation and fibrosis progress in CHC, whereas IL-17 and IL-25 may be used as biomarkers for the development of hepatocellular carcinoma.


2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Alijan Ahmadi Ahangar ◽  
Payam Saadat ◽  
Sona Niroomand ◽  
Shayan Alijanpour ◽  
Reza Sohrabnezhad ◽  
...  

Background. Stroke is the second leading cause of death worldwide. The role of zinc as a new predictor of stroke was considered. Methods. This prospective study was conducted in Ayatollah Rouhani Hospital within a year on 100 stroke and 100 control patients. Findings. The difference in zinc serum level in two groups was significant (deficiency: 3 (3%) in patients versus 20 (20%) in control group, normal: 25 (25%) versus 54 (54%), and increased level: 72 (72%) versus 26 (26%); p<0.001). Difference in zinc serum levels was statistically significant with ischemic heart disease (deficiency: 0 cases (0%), normal: 8 cases (24%), increased level: 24 cases (75%), p=0.003). Increases in zinc serum level were significantly correlated with the frequency of hemorrhagic and ischemic patients (deficiency: 3 (3.3%) hemorrhagic versus 0 (0%) ischemic; normal: 19 (21%) versus 6 (60%), increased level: 68 (75.6%) versus 4 (40%); p=0.025). Regression logistics showed that ischemic heart disease (p<0.001; OR = 28.29, %95 CI: 5.53; 144.87), hyperlipidemia (p<0.001; OR = 0.26, %95 CI: 0.12; 0.56), and zinc serum level (p<0.001, OR = 15.53, %95 CI: 4.03; 59.83) each had a significant role. Conclusions. Babol stroke patients are prone to increased zinc serum level as a new parameter. Ischemic heart disease, increased levels of zinc, and hyperlipidemia were found to be probable predictor factors for stroke in Babol.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Rodolfo Pessato Timoteo ◽  
Marcos Vinicius da Silva ◽  
Camila Botelho Miguel ◽  
Djalma Alexandre Alves Silva ◽  
Jonatas Da Silva Catarino ◽  
...  

Pemphigus vulgaris (PV) is an autoimmune disease characterized by the presence of IgG autoantibodies against desmoglein-3. Despite the variety of findings, the chemokine and cytokine profiles that characterize the immune response in the disease are still poorly explored. Thus, 20 PV patients and 20 controls were grouped according to gender, ethnicity, place of residence, and clinical parameters of the disease. Then, the levels of chemokines and of Th1/Th2/Th17/Treg/Th9/Th22-related cytokines were assessed in the serum. PV patients had higher levels of inflammatory Th1/Th17 cytokines (IFN-γ, IL-17, and IL-23), as well as higher levels of CXCL8 and reduced levels of Th1/Th2-related chemokines (IP-10 and CCL11). However, no differences in the levels of IL-2, IL-6, TNF-α, IL-1β, IL-4, IL-9, IL-12, TGF-β, IL-33, MCP-1, RANTES, and MIP-1α were found between PV patients and their control counterparts. Furthermore, PV patients with skin lesions had higher serum levels of IL-6 and CXCL8 when compared to PV patients without lesions. Taken together, our findings describe the role of cytokines and chemokines associated with Th1/Th17 immune response in PV patients. Finally, these data are important for better understanding of the immune aspects that control disease outcome, and they may also provide important information about why patients develop autoantibodies against desmogleins.


2020 ◽  
Vol 14 (12) ◽  
pp. 1109-1119
Author(s):  
Hemant J Vira ◽  
Vandana D Pradhan ◽  
Vinod D Umare ◽  
Ajay K Chaudhary ◽  
Anjali G Rajadhyksha ◽  
...  

Aim: To investigate the possible association between MMP-2 (−1575 G/A, −1306 C/T) and its inhibitor TIMP-2 (−418 G/C) functional polymorphisms with development of severity in systemic lupus erythematosus (SLE) patients. Materials & methods: 150 SLE patients and matched healthy controls were recruited. Polymorphisms were detected by PCR-RFLP and serum levels by ELISA. Results: Mean MMP-2 and TIMP-2 serum level and mRNA expression were significantly increased in SLE cases as compared with controls (p < 0.0001). The concomitant presence of both MMP-2 1575A and its inhibitor TIMP-2 418C alleles synergistically increased the risk of SLE by 3.25-fold (CI: 1.44–7.34, p = 0.003). Conclusion: MMP-2, TIMP-2 and MMP-2/TIMP-2 ratios may act as biomarkers for susceptibility to SLE.


2017 ◽  
Vol 95 (4) ◽  
pp. 474-481 ◽  
Author(s):  
Rehab A. Karam ◽  
Haidy E. Zidan ◽  
Mohamed H. Khater

Although genetics plays an essential role in the pathogenesis of vitiligo, vitiligo pathogenesis is still unclear. Our aim was to investigate the role of IFN-γ expression and polymorphism in vitiligo susceptibility and whether intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor (TNF)-α, and TNF-β play a role in vitiligo pathogenesis as important inflammatory parameters. Eighty-five patients with vitiligo and 90 controls were investigated for IFN-γ gene expression by quantitative real-time PCR and genotyped for IFN-γ +874T/A (rs2430561) and IFN-γ +2109A/G (rs1861494) gene polymorphisms by sequence-specific primer (SSP)-PCR and PCR-restriction fragment length polymorphism (RFLP), respectively. Serum levels of inflammatory parameters were measured using ELISA. Frequencies of the +874 TT genotype and T allele were significantly higher in patients with active vitiligo than in stable patients (P = 0.01 and 0.03, respectively). Calculation of odds ratio suggested a 1.7-fold increased risk of vitiligo in individuals having the TA haplotype. We observed overexpression of IFN-γ mRNA with elevated serum levels of IFN-γ, ICAM-1, TNF-α, and TNF-β in patients with vitiligo when compared with the control group (P = 0.001, for all). In addition, these levels were elevated in patients with active vitiligo compared with stable patients with vitiligo (P = 0.008, 0.006, 0.01, 0.01, and 0.03, respectively), which suggests the involvement of these cytokines in disease activity. In conclusion, IFN-γ is a promising immunological marker in vitiligo pathogenesis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Georgi Vasilev ◽  
Irena Manolova ◽  
Mariana Ivanova ◽  
Iskren Stanilov ◽  
Lyuba Miteva ◽  
...  

AbstractWe aimed to analyze serum pro-inflammatory profiles of female rheumatoid arthritis (RA) patients and compare them with healthy women to establish the relative importance of pro-inflammatory cytokines in RA and their relation with different treatment regimens. Levels of six cytokines were determined by ELISA assays. A supervised dimensionality reducing approach (PLS-DA Analysis) was applied. All of the cytokines assayed were significantly elevated in the sera of RA female patients than healthy controls with fold change: 21-fold for IL-6; 6.1-fold for IL-17A; 2.5-fold for IL-23; 2.3-fold for IL-18; 1.94-fold for TNF-α; 1.7-fold for IL-12p40. According to the results of the PLS-DA analysis, IL-17A, IL-18, and TNF-α were of higher importance rank compared to IL-23 and IL-12p40. Women in the early stage of RA displayed significantly elevated IL-17A levels than those with longer disease duration: 8.04 pg/ml [8.04–175.3] vs 4.64 pg/ml [2.95–13.31], p = 0.007. IL-6 serum levels were related to higher disease activity. We have demonstrated altered cytokine production within female RA patients on different treatment regimens. Those on Tocilizumab therapy showed elevated IL-6 levels and decreased IL-17A versus the rest of the patients’ subgroups. In conclusion, our data support the pivotal role of IL-18 in addition to IL-6, IL-17A, and TNF-α as the hierarchical cytokines in the pathogenesis of RA, particularly valid for women. Therapy with biological agents targeting IL-18 in addition to the Th17 axis may be an adequate approach in RA patients.


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