Proanthocyanidins: novel treatment for psoriasis that reduces oxidative stress and modulates Th17 and Treg cells.
Redox report : communications in free radical research
Psoriasis is a common, chronic, inflammatory skin disease that affects 2%-4% of the global population. Recent studies have shown that increased oxidative stress (OS) and T-cell abnormalities are central to the pathogenesis of this disease. The resulting reactive oxygen species (ROS) induces proliferation and differentiation of Th17/Th1/Th22 cells and inhibits the anti-inflammatory activities of regulatory T lymphocytes (Treg). Subsequent secretions of inflammatory cytokines, such as interleukin (IL)-17, IL-22, tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ), and vascular endothelial growth factor (VEGF), stimulate keratinocyte proliferation and angiogenesis. Proanthocyanidins are a class of flavonoids from plants and fruits, and have various antioxidant, anti-inflammatory, and anti-angiogenic properties. Numerous reports have demonstrated therapeutic effects of proanthocyanidins for various diseases. Among clinical activities, proanthocyanidins suppress cell proliferation, prevent OS, and regulate Th17/Treg cells. Because the pathogenesis of psoriasis involves OS and T cells dysregulation, we reviewed the effects of proanthocyanidins on OS, Th17 and Treg cell activities, and keratinocyte proliferation and angiogenesis. Data from multiple previous studies warrant consideration of proanthocyanidins as a promising strategy for the treatment of psoriasis.
10.1080/13510002.2018.1462027
Herpes simplex virus type I-infected disorders alter the balance between Treg and Th17 cells in recurrent herpes labialis patients.
Mei Xian-Xian,Lei Shan-Shan,Xu Li,Wu Shan,Gu Huan-Peng,Du Yu,Zhao Ting,Xie Guan-Qun,Fan Yong-Sheng,Pan Xiao-Ping,Bao Jie
International journal of immunopathology and pharmacology
Recurrent herpes labialis (RHL) is a common skin disease that is often caused by herpes simplex virus type I (HSV-1), but its immunology and pathogenesis remain unclear. The balance of Th17/Treg cells is crucial for maintaining immune homeostasis. This study aimed to investigate whether the balance of Th17/Treg cells and related cytokines may be a determinant occurrence in patients with RHL. This is a clinical experimental research based on clinical observation and analysis. We collected RHL patients from the outpatient clinic of the Department of Dermatology of Zhejiang Chinese Medical University (Hangzhou, China) in 2017, conducted questionnaire survey and signed informed consent. Peripheral blood was collected from 30 patients with RHL and 30 healthy volunteers. Flow cytometry was used to detect the percentages of Treg cells and Th17 cells. Protein microarrays coated with 20 cytokines related to T-cell subsets were performed. Enzyme-linked immunosorbent assay (ELISA) assay was conducted to further verify the expression levels of the cytokines that were screened by protein microarrays. Percentages of Th17/Treg cells in peripheral blood of RHL patients were significantly increased compared to those in healthy volunteers. The fold changes of GM-CSF, IL-4, TGF-β, IL-12, IL-10, IL-17F, and TNF-α were significantly increased compared with healthy volunteers. In addition, the expression of IL-4, IL-10, and TGF-β in the serum of RHL patients increased significantly. Our results indicated an imbalance of Th17/Treg cells in RHL, and this imbalance is probably an important factor in the occurrence, development, and recovery of RHL.
10.1177/2058738420933099
TNF-α enhance Th2 and Th17 immune responses regulating by IL23 during sensitization in asthma model.
Lee Hyun Seung,Park Heung-Woo,Song Woo-Jung,Jeon Eun Young,Bang Boram,Shim Eun-Jin,Moon Hyung-Geun,Kim Yoon-Keun,Kang Hye-Ryun,Min Kyung-Up,Cho Sang-Heon
Cytokine
BACKGROUND:TNF-α has been postulated to be a critical mediator contributing to airway inflammation. The purpose of this study was to evaluate the role of TNF-α in the induction of Th17 and Th2 cells related to asthma pathogenesis. OBJECTIVE:To evaluate detailed mechanisms for the modulation of IL-23 by TNF-α in sensitization period. METHODS:During sensitization period, 10μg of rat anti-mouse TNF-α mAb was intravenously administrated one hour before the application of OVA and 0.1μg of LPS. To see the relation between TNF-α and associated effectors cytokine, we replenished TNF-α KO mice with IL-23 during sensitization period. To assess cellular resources, CD11c+ cells isolated from lung tissue after sensitization were treated with anti-TNF-α Ab. RESULTS:Treatment of anti-TNF-α mAb during sensitization period significantly reduced airway eosinophilia, serum OVA-specific IgE levels and methacholine AHR compared to isotype Ab. Anti-TNF-α mAb treated mice showed significant reduction in the levels of IL-23 after sensitization in bronchoalveolar lavage fluid (BALF) as well as IL-17A, IL-4 levels in BALF after challenge compared with isotype Ab treated mice. Supplementation of IL-23 in TNF-α KO mice resulted in complete restoration of eosinophilic airway inflammation, AHR, and IL-17A and IL-4 expression in CD4+ T cells. Anti-TNF-α mAb treatment after sensitization significantly diminished the population of IL-23p19-secreting CD11c+ cells in lung. CONCLUSION:TNF-α plays an important role in the development of airway inflammation by enhancing IL-23/Th17 and Th2 immune responses.
10.1016/j.cyto.2015.12.001
Evaluation of TNF-α serum level in patients with recalcitrant multiple common warts, treated by lipid garlic extract.
Kenawy Soha,Mohammed Ghada Farouk,Younes Soha,Elakhras Atef Ibrahim
Dermatologic therapy
No universal consensus about optimal modality for treating the recalcitrant multiple common warts (RMCW). The objective of the study was to evaluate the immunological mechanisms and clinical therapeutic effect of using lipid garlic extract (LGE) in the treatment of RMCW. The study included 50 patients with RMCW. They were randomly assigned into two groups: the first group (25 patients) received LGE, and the second group (25 patients) received saline as a control group. In both groups, treatments were made to single lesions, or largest wart in case of multiple lesions, until complete clearance of lesions or for a maximum of 4 weeks. Blood serum was taken at pre-study and at the fourth week to measure tumor necrosis factor alpha (TNF-α) level. A significant difference was found between the therapeutic responses of RMCW to LGE antigen and saline control group (p < 0.001). In the LGE group, complete response was achieved in 96% of patients presenting with RMCW. There was a statistically nonsignificant increase in TNF-α of LGE group versus saline group. No recurrence was observed in the LGE group. LGE as an immunotherapy is an inexpensive, effective, and safe modality with good cure rates for treatment of RMCWs, when other topical or physical therapies have failed.
10.1111/dth.12136
Serum level of interleukin-22 in patients with cutaneous warts: A case-control study.
Journal of cosmetic dermatology
BACKGROUND:Warts are viral cutaneous infections caused by human papilloma virus (HPV), presented by verrucous growth over the skin surface. The immune response is considered to play a crucial role in HPV clearance. It depends on intact cellular immunity including natural killer (NK) cell and cytotoxic T cells. It has been clarified that T-helper (Th) 1 cytokines (interleukin (IL)-2, interferon-γ, and tumor necrosis factor-a) and IL-17 are involved in HPV clearance. IL-22 is one of IL-10 family of cytokines produced by NK cells, Th1, Th17, and Th22 cells. In the skin, IL-22 reduces keratinocyte cornification and enhances keratinocyte production of antimicrobial peptides. IL-22 overexpression has been demonstrated in various viral infections and skin inflammatory disorders. AIM:The aim of this study was to assess serum levels of IL-22 in patients with warts and its association with their different clinical characteristics. METHODS:The study included 20 patients with warts and 20 control subjects. Serum concentration of IL-22 was measured by enzyme-linked immune sorbent assay. RESULTS:Serum levels of IL-22 were significantly higher in patients with warts than in control subjects (P < .001). The levels were significantly higher in patients with recurrent warts after prior treatment than in patients with first-time warts (P = .007). Moreover, a significant positive correlation was detected between serum levels of IL-22 and the number of warts (P = .017). CONCLUSION:Serum level of IL-22 was elevated in patients with warts. Thus, IL-22 may have a crucial role in the antiviral immune response against this infection.
10.1111/jocd.13779
Possible role of interleukin-17 and macrophage migration inhibitory factor in cutaneous warts.
El-Hamd Mohammed Abu,Assaf Hanan A,Nada Essam A
Journal of cosmetic dermatology
BACKGROUND/OBJECTIVES:Cutaneous warts (CW), or verrucae, are benign proliferation of skin that result from infection with human papilloma viruses. Cellular immune reactivity plays a significant role in wart regression. The aim of this study was to elucidate the cellular immune status of patients with CW through measurements of their serum levels of interleukin-17 (IL-17) and macrophage migration inhibitory factor (MIF,) and, identify the possible role of IL-17 and MIF in CW. We assessed serum IL-17 and MIF levels in patients with different forms of CW and compare the results with controls. PATIENT AND METHODS:Serum levels of IL-17 and MIF were measured using commercially available ELISA assay kits in 60 patients with CW and 20 healthy controls. RESULTS:Serum levels of IL-17 and MIF were significantly lower in patients with CW when compared with the controls (P-value <.01, <.05, respectively). There was nonsignificant correlation between IL-17 and MIF. CONCLUSION:Low IL-17 and MIF levels may have a contributory role in occurrence, maintenance, severity, and recurrence of different types of CW which depend mainly on the defect of cell-mediated immunity. This may shed new light on nontraditional strategies for the future medical treatments of CW through regulation of IL-17 and MIF.
10.1111/jocd.12472
Gingival crevicular fluid levels of interleukin-18 and tumor necrosis factor-alpha in type 1 diabetic children with gingivitis.
Keles Sultan,Anik Ahmet,Cevik Ozge,Abas Burcin Irem,Anik Ayse
Clinical oral investigations
OBJECTIVE:This study aimed to evaluate the levels of interleukin-18 and tumor necrosis factor-alpha in gingival crevicular fluid of diabetic children with gingivitis. METHODOLOGY:Eighty-eight children (44 with type 1 diabetes mellitus and 44 systemically healthy) were recruited for the study. The children were divided into four subgroups based on their periodontal and systemic condition: (1) systemically and periodontally healthy children (H), (2) systemically healthy children with gingivitis (G), (3) periodontally healthy children with T1DM (T1DM + H), and (4) children with T1DM and gingivitis (T1DM + G). The plaque index, gingival index, probing pocket depth, and GCF volume were recorded. The IL-18 and TNF-α levels in GCF were determined by ELISA. RESULTS:The clinical periodontal parameters, GCF IL-18 level, and TNF-α level were similar between diabetic and systemically healthy children (p > 0.05). The gingivitis subgroups had a significantly higher GI, PI, PPD, GCF volume, and TNF-α total amounts than the H subgroups (p < 0.0001). The IL-18 concentrations in the gingivitis subgroups were significantly lower than in the periodontally healthy subgroups. CONCLUSIONS:In diabetic children with good metabolic control, T1DM did not affect the GCF levels of IL-18 and TNF-α in the presence of gingivitis. However, increased GCF TNF-α levels in children with gingivitis confirm that TNF-α is closely related to gingival inflammation. CLINICAL RELEVANCE:Type 1 diabetes mellitus is not associated with GCF interleukin-18 and tumor necrosis factor-alpha levels in children with gingivitis.
10.1007/s00784-020-03238-z
Serum Visfatin, Adiponectin, and Tumor Necrosis Factor Alpha (TNF-α) Levels in Patients with Psoriasis and their Correlation with Disease Severity.
Sereflican Betul,Goksugur Nadir,Bugdayci Guler,Polat Mualla,Haydar Parlak Ali
Acta dermatovenerologica Croatica : ADC
Psoriasis is a chronic, autoimmune, and inflammatory disease of unknown etiology, characterized by T lymphocyte mediated keratinocyte proliferation. In recent years the relationship between psoriasis and adipose tissue cytokines has been reported. Psoriasis as a triggering factor for the immune and metabolic disorders can be associated with diabetes mellitus, abnormal lipid metabolism, and metabolic syndrome. In this study we assessed the adipose tissue cytokines visfatin, adiponectin, and tumor necrosis factor-α (TNF-α) levels in psoriasis patients and evaluated the relationship between disease severity and cytokines. The study included 42 patients with psoriasis and 42 healthy individuals. Visfatin, adiponectin, and TNF-α levels were measured in both the psoriasis and the control group. The disease severity index was assessed in psoriatic patients by means of PASI. The relationship between visfatin, adiponectin, TNF-α, PASI score, and obesity was evaluated. When serum TNF-α, adiponectin, and visfatin levels of the patient group were compared with those of the control group, the TNF-α levels were statistically higher (p = 0.00) and the adiponectin levels were statistically lower (p = 0.024). The visfatin levels were higher in the psoriatic patients compared to the control group, but this difference was not statistically significant (p = 0.73). The relationship between PASI-TNF-α and between PASI-adiponectin was statistically significant (p = 0.009 and p = 0.004). A positive correlation was observed between body mass index (BMI) and visfatin (p = 0.031). These results indicate that TNF-α and adiponectin play a part in psoriasis etiopathogenesis and can be used as parameters to evaluate the severity of the disease. However, the role of visfatin in psoriasis pathogenesis is unclear. Further clinical studies are needed to clarify the effect of visfatin in psoriatic patients.
Role of IL-21 signaling pathway in transplant-related biology.
Shi Xiaoyu,Que Risheng,Liu Baoqing,Li Mingming,Cai Jinzhen,Shou Dawei,Wen Liang,Liu Dahai,Chen Li,Liang Tingbo,Gong Weihua
Transplantation reviews (Orlando, Fla.)
Since pro-inflammatory cytokine IL-21 and its receptor (IL-21R) are closely involved in regulating both innate and adaptive immune responses, it is conceivable that they may play important roles in the field of organ transplantation. IL-21/IL21-R regulates immune activities of CD8+ T cells, Tfh cells, Th17 cells, B cells, NK cells, dendritic cells and stimulates dendritic cells to produce high level of IL-6, TNF-alpha, and CCL2. However, their roles and underlying mechanisms remain obscure. Our present study is the first describing the role of IL-21 signaling pathway in transplant biology. It was found that IL-21/IL-21R signaling pathways contribute to the processes of ischemia/reperfusion and acute rejection of liver or kidney transplantation. IL-21 is capable of regulating B cell function and immunoglobulin production, driving CD8+ T cell expansion, regulating Th17 and dendritic cell function. Deficiency of IL-21 may cause autoimmunity and infectious disease in clinical-scenario patients. It is known that CD8+ T cells, Th17, and dendritic cells are closely involved in cardiac transplant tolerance. Our own original experimental research on mouse cardiac transplantation manifested that allograft survival could be significantly prolonged in the IL-21R deficient recipients. All these can deepen our understanding of immunobiological role of IL-21 and its receptor in the field of transplantation. Intervention of IL-21 signaling pathway may apparently regulate immunoresponses in vivo, which can be subsequently utilized as a therapeutic strategy in clinic.
10.1016/j.trre.2015.06.003