Interleukin-17 and interleukin-23 inhibitors in the treatment of pustular psoriasis / 中华皮肤科杂志

Pustular psoriasis is a serious life-threatening disease, and patients usually show poor response to traditional treatments. In recent years, interleukin-17 and interleukin-23 inhibitors have shown favorable efficacy in the treatment of psoriasis. This review summarizes the latest progress in interleukin-17 and interleukin-23 inhibitors for the treatment of pustular psoriasis.

Application of the interleukin-23 inhibitor guselkumab in the treatment of psoriasis / 中华皮肤科杂志

Guselkumab is the first monoclonal antibody that selectively targets interleukin (IL) -23. Several randomized controlled clinical trials have demonstrated that it is highly effective and safe in the treatment of moderate to severe plaque psoriasis, and can significantly improve the quality of life of patients. This review summarizes the action mechanisms of IL-23 and guselkumab, as well as the application of guselkumab in the treatment of psoriasis.

Expression and significance of IL-17, IL-23 and IL-22 in rats with Klebsiella pneumoniae pneumonia / 国际生物医学工程杂志

Objective:To analyze the expression and significance of interleukin-17 (IL-17), IL-23 and IL-22 in Klebsiella pneumoniae (KPN) pneumonia in rats. Methods:A total of 40 male SPF rats were randomly divided into the control group and the experimental group according to the simple number random table method, with 20 rats in each group. The control group was simultaneously dropped with 2 mL normal saline, while the experimental group was inoculated with a 2 mL suspension of 0.9×10 9 CFU/mL. The lung tissue was taken for pathological and bacteriological examination. Arterial partial pressure of oxygen (PaO 2), serum IL-17, IL-23 and IL-22 levels were detected after surgery for 4 h, 1 d, 3 d and 5 d. White blood cell count (WBC) and absolute neutrophil count (ANC) were performed in bronchoalveolar lavage fluid (BALF), and the relevance between IL-17, IL-23, IL-22 and PaO 2, and WBC, ANC in BALF was analyzed. Results:After surgery for 4 h, 1 d, 3 d and 5 d, the CFU count of lung tissue in experimental group rats decreased over time. PaO 2 in experimental group was significantly lower than that in the control group after surgery for 4 h, 1 d, 3 d and 5 d ( P<0.05), while WBC and ANC in BALF in the experimental group were significantly higher at the same time ( P<0.05). The levels of IL-17 and IL-23 in serum in the experimental groups were significantly higher than those in the control group after surgery for 4 h, 1 d, 3 d and 5 d ( P<0.05), and the levels of IL-22 in serum in the experimental groups were significantly lower than those in the control group at the same time ( P<0.05). Pearson analysis showed that IL-17 and IL-23 were negatively correlated with PaO 2 ( P<0.05) and positively correlated with WBC and ANC ( P<0.05). IL-22 was positively correlated with PaO 2 ( P<0.05), and negatively correlated with WBC and ANC ( P<0.05). Conclusions:Serum IL-17, IL-23, and IL-22 levels were significantly altered during the course of KPN rats, and serum IL-17, IL-23, and IL-22 levels were correlated with severity of illness.

Effect of interleukin-23R overexpression on Th17/Treg balance in experimental autoimmune uveitis mice / 中华眼底病杂志

Objective:To investigate the effect of interleukin (IL)-23 receptor (IL-23R) overexpression on the balance of T helper 17 (Th17 cells)/regulatory T cells (Treg cells) in experimental autoimmune uveitis (EAU) mice.Methods:Twelve 8-week-old female C57BL/6J mice were randomly divided into LV-Ctrl group and LV-IL-23R group, with 6 mice in each group. Two groups of mice were injected with LV-Ctrl and LV-IL-23R lentiviruses through the tail vein, respectively; 7 days after injection, the EAU mouse model was established by active immunization with vitamin A-binding protein 1-20 between photoreceptors. Starting from 13 days after immunization, the fundus of the mice was observed by indirect ophthalmoscopy every 2 days and clinical scores were performed; 30 days after immunization, hematoxylin-eosin staining was used to observe the histopathological changes of mouse retina. The levels of IL-17 in serum of the two groups of mice were detected by enzyme-linked immunosorbent assay; the proportion of Th17 cells and Treg cells was detected by flow cytometry. The relative mRNA expression of IL-23R, IL-17, retinoic acid-related orphan receptor γt (RORγt), IL-10 and forkhead transcripyion factor p3 (Foxp3) were detected by real-time quantitative polymerase chain reaction. Comparisons between groups were performed using repeated measures analysis of variance, independent samples Mann-Whitney U test, and independent samples t test. Results:Compared with the LV-Ctrl group, the retinal inflammatory reaction of the LV-IL-23R group was more severe. At 13 days after immunization, there was no significant difference in fundus inflammation scores between LV-IL-23R group and LV-Ctrl group ( t=-2.001, P=0.058); 15-29 days after immunization. The fundus inflammation scores of LV-IL-23R group were higher than those of LV-Ctrl group, and the difference was statistically significant ( t=-4.429,-6.578, -7.768, -10.183, -6.325, -7.304, -4.841, -6.872; P<0.001). Histopathological examination showed that the infiltration of inflammatory cells in the fundus increased, the retinal structure was damaged more seriously, and the histopathological score was significantly increased, and the difference was statistically significant ( t=-4.339, P=0.001). Compared with the LV-Ctrl group, the relative expression of IL-23R mRNA in the spleen of the LV-IL-23R group was significantly increased, and the difference was statistically significant ( Z=2.087, P=0.037). The relative expression of IL-17 and RORγt mRNA increased, while the relative expression of IL-10 and Foxp3 mRNA decreased, and the differences were statistically significant ( t=-6.313,-5.922, 4.844, 7.572; P=0.003, 0.004, 0.008, 0.002). Compared with the LV-Ctrl group, the level of IL-17 in the serum of the mice in the LV-IL-23R group was significantly increased, and the difference was statistically significant ( t=-5.423, P=0.002); the proportion of Th17 cells in the spleen and lymph nodes was significantly increased, whereas, the proportion of Treg cells was significantly reduced, and the difference was statistically significant ( t=-4.290, 3.700; P=0.002, 0.006). Conclusion:IL-23R overexpression can promote Th17/Treg imbalance in EAU mice, and aggravate the clinical and pathological manifestations of EAU.

High IL-23+ cells infiltration correlates with worse clinical outcomes and abiraterone effectiveness in patients with prostate cancer / 亚洲男科学杂志(英文版)

Individualized treatment of prostate cancer depends on an accurate stratification of patients who are sensitive to various treatments. Interleukin-23 (IL-23) was reported to play a significant role in prostate cancer. Here, we aimed to explore the clinical value of IL-23-secreting (IL-23+) cells in prostate cancer patients. We evaluated interleukin-23A (IL-23A) expression in The Cancer Genome Atlas database and retrospectively enrolled 179 treatment-naïve metastatic prostate cancer patients diagnosed in our institute between June 2012 and December 2014. IL-23+ cells were stained and evaluated via immunohistochemistry. Further, survival and multivariate Cox regression analyses were conducted to explore the prognostic value of IL-23+ cells. We found that IL-23A expression correlated with disease progression, while IL-23+ cells were clearly stained within prostate cancer tissue. Patients with higher Gleason scores and multiple metastatic lesions tended to have more IL-23+ cell infiltration. Further analyses showed that patients with higher levels of IL-23+ cells had significantly worse overall survival (hazard ratio [HR] = 2.996, 95% confidence interval [95% CI]: 1.812-4.955; P = 0.001) and a higher risk of developing castration resistance (HR = 2.725, 95% CI: 1.865-3.981; P = 0.001). Moreover, subgroup analyses showed that when patients progressed to a castration-resistant status, the prognostic value of IL-23+ cells was observed only in patients treated with abiraterone instead of docetaxel. Therefore, we showed that high IL-23+ cell infiltration is an independent prognosticator in patients with metastatic prostate cancer. IL-23+ cell infiltration may correlate with abiraterone effectiveness in castration-resistant prostate cancer patients.

The Relationship between Serum IL-17 and IL-23 Levels, and Other Disease Activity Parameters in Patients with Behçet's Disease

ABSTRACT Objective: To investigate the relationship between disease activity and the involvement of Behçet's disease (BD) and serum levels of interleukin (IL)-17 and IL-23. Methods: Sixty patients with BD and 20 healthy control group subjects were included in this study. The patients were divided into four groups according to clinical findings as follows: entero-Behçet, mucocutaneous-Behçet, neuro-Behçet and vascular-Behçet. The serum levels of the IL-17 and IL-23 levels were evaluated using enzyme-linked immunosorbent assay. Results: Of the BD patients, 15 (25%) had active disease and 45 (75%) had inactive disease. The serum levels of IL-23 and IL-17 were statistically significantly higher in the patients with BD than in the control groups (p < 0.05). A significant relationship was also observed between the disease activity, and both the erythrocyte sedimentation rate and the C-reactive protein levels (p < 0.05). The mean serum levels of IL-17 and IL-23 in patients with active disease were 0.07 ± 0.25 pg/ml and 36.0 ± 30.5 pg/ml, respectively. There was no statistically significant relationship between the disease activity and the serum levels of IL-17 and IL-23 (p > 0.05). There were also statistically significant relationships between the disease activity and uveitis, retinal vasculitis or superficial thrombophlebitis. Conclusion: No relationship was found between BD and serum levels of the IL-17 and the IL-23.

The Effect of Interleukin 23 Levels on Clinical and Laboratory Parameters of Patients with Ankylosing Spondylitis

ABSTRACT Objective: In the present study, we aimed to investigate the relationship between interleukin 23 (IL-23) and the clinical and laboratory parameters in patients with ankylosing spondylitis (AS). Ankylosing spondylitis causes structural and functional inability, particularly in the axial skeleton, and results in the inflammatory lower back pain. At the same time, we aimed to investigate the relationship between IL-23 levels and disease related variables in patients with AS. Methods: A total of 38 patients with AS (33 males and 5 females) and 42 healthy controls (32 males and 10 female) were enrolled in the study. The demographic characteristics of the participants were recorded. As laboratory findings, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and IL-23 values were noted. Bath AS Disease Activity Index, Bath AS Functional Index, Visual Analogue Scale, and AS Quality of Life scales of the patients were measured. Results: The mean age of the AS group and the control subjects was 32.4 ± 7.06 and 30.0 ± 6.24 years, respectively. The ESR, CRP and IL-23 levels were significantly higher in the AS group compared to those of the healthy controls (p < 0.001, p < 0.013, p < 0.012, respectively). There was a significant correlation between ESR, CRP, and IL-23 levels in patients with AS (r = 0.328, p = 0.030 and r = 0.392, p = 0.008, respectively). While 12 subjects (31.5%) were positive for peripheral arthritis, 26 patients were negative (68.4%). The IL-23 levels were significantly higher in the group that was positive for peripheral arthritis (p < 0.05). Conclusion: Interleukin 23 may play a role in the progression and/or pathogenesis of AS and is most likely involved in the joint problems independent of the classic inflammatory response measures.

Mechanisms underlying microRNA-125a-mediated inhibition of proliferation of HaCaT cells by targeting the interleukin 23 receptor signaling pathway: a preliminary study / 中华皮肤科杂志

Objective:To explore the mechanism underlying microRNA (miR) -125a-mediated inhibition of proliferation of keratinocytes.Methods:After 24-hour pretreatment with interleukin (IL) -23, human HaCaT keratinocytes were divided into miR-125a group and miR-NC group transfected with a miR-125a overexpression plasmid and a control plasmid, respectively. Cell counting kit-8 (CCK8) assay was performed to evaluate the proliferative ability of HaCaT cells in the two groups at 0, 24, 48 and 72 hours after transfection, real-time fluorescence-based quantitative PCR to determine the mRNA expression of miR-125a and IL-23 receptors (IL-23R) in the two groups 24 hours after transfection, and Western blot analysis to determine the protein expression of IL-23R, Janus kinase 2 (JAK2) , protein kinase B (AKT) and phosphorylated AKT (p-AKT) in the two groups 48 hours after transfection. Dual-luciferase reporter assay was performed to verify the targeting relationship between miR-125a and IL-23R. Comparison of means between two groups was carried out by using t test, and changes in the proliferative ability of HaCaT cells over time were evaluated by using repeated measures analysis of variance. Results:After plasmid transfection, the relative expression of miR-125a was significantly higher in the miR-125a group (6.377 ± 0.745) than in the miR-NC group (0.700 ± 0.222; t=7.305, P=0.002) . At 0, 24 and 48 hours after transfection, there was no significant difference in cellular proliferative ability between the miR-125a group and the miR-NC group ( t=0.663, 0.623 and 1.930, respectively, all P > 0.05) ; at 72 hours after transfection, the cellular proliferative ability was significantly lower in the miR-125a group than in the miR-NC group ( t=4.407, P < 0.05) . The IL-23R mRNA expression was significantly lower in the miR-125a group than in the miR-NC group ( t=3.082, P < 0.05) . Compared with the miR-NC group, the miR-125a group showed significantly decreased protein expression of IL-23R, JAK2 and p-AKT ( t=11.715, 6.996, 12.424, P < 0.001,=0.002, < 0.001, respectively) . Dual-luciferase reporter assay showed targeted binding of miR-125a to IL-23R. Conclusion:MiR-125a may inhibit the proliferation of keratinocytes by negatively regulating the IL-23R/JAK2/AKT signaling pathway.

Influência da laserterapia de baixa intensidade no processo inflamatório e na imunomarcação da interleucina­23 e do fator indutor de hipóxia 1-alfa no tecido pulpar de dentes clareados / Influence of low-level laser therapy on the inflammatory process and immunolabeling of interleukin-23 and hypoxia-inducing factor 1-alpha in the pulp tissue of bleached teeth

Introdução: O uso do laser infravermelho (LIV) através da fotobiomodulação, tem demonstrado efeitos benéficos aos tecidos. Objetivos: Avaliar a influência do LIV sobre o processo inflamatório, por meio da imunomarcação da interleucina próinflamatória IL-23, e sobre a angiogênese, por meio da imunomarcação do fator induzível por hipóxia-1 alfa (HIF-1α), no tecido pulpar de dentes clareados. Materiais e métodos: Quarenta ratos Wistar foram distribuídos aleatoriamente em 4 grupos de 20 hemi-maxilas cada: Grupo Controle ­ recebeu o tratamento com o gel placebo; Grupo Cla - recebeu 30 minutos do gel clareador H2O2 a 35%; Grupo LIV ­ recebeu uma aplicação de LIV (808 nm, 30 segundos, 3J); Grupo Cla-LIV ­ imediatamente após a aplicação do H2O2 a 35%, recebeu uma aplicação de LIV, como descrito no grupo LIV. Após 2 e 30 dias (n = 10), os animais foram eutanasiados e as maxilas removidas e processadas para avaliação histológica (H.E.) e imunoistoquímica. Forma de análise: Os cortes teciduais seriados e com espessura de 5 µm corados em H.E. foram avaliados por escores atribuídos à inflamação, e a análise imunoistoquímica foi realizada através de escores atribuídos à imunomarcação. Os dados foram submetidos aos testes de Wilcoxon e Mann Whitney (p < 0,05). Resultados: Aos 2 dias, houve inflamação severa e necrose nos terços oclusal e médio do tecido pulpar no grupo Cla, diferente do grupo Cla-LIV com inflamação leve à moderada (p < 0,05). No terço cervical, houve inflamação moderada a severa no grupo Cla, e leve no grupo Cla-LIV (p < 0,05). Aos 30 dias, houve ausência de inflamação e os grupos clareados apresentaram deposição de dentina terciária. Em relação à IL-23, aos 2 dias foi observada imunomarcação severa no grupo Cla e moderada no grupo Cla-LIV (p < 0,05); aos 30 dias, houve redução na imunomarcação de IL-23 nos grupos clareados, onde o grupo Cla apresentou imunomarcação moderada, e o grupo Cla-LIV leve imunomarcação, sem diferença significante (p > 0,05). HIF-1α foi mais presente aos 2 dias no grupo Cla, sem diferença significativa com Cla-LIV (p > 0,05). Foi observada diferença entre os grupos clareados e seus respectivos controles, que não apresentaram imunomarcação (p < 0,05); aos 30 dias, o grupo Cla apresentou redução na imunomarcação para HIF-1α, enquanto o grupo Cla-LIV apresentou aumento da imunomarcação, mas a diferença permaneceu apenas entre os grupos clareados e seus controles (p > 0,05). Conclusão: O laser infravermelho minimizou o infiltrado inflamatório e a imunomarcação de IL-23 no tecido pulpar após a clareação dentária, mas não influenciou a imunomarcação de HIF-1α(AU)

Introduction: The use of infrared laser (IRL) through photobiomodulation has shown beneficial effects on tissues. Objectives: To evaluate the influence of LLL on the inflammatory process, by immunolabeling IL-23 pro-inflammatory interleukin, and on angiogenesis, by immunolabeling hif-1 alpha inducible factor (HIF-1α) in the pulp tissue of bleached teeth (HIF-1α). Materials and methods: Forty Wistar rats were randomly divided into 4 groups of 20 hemimaxilla each: control group - received treatment with placebo gel; Ble group - received 30 minutes of 35% H2O2 bleaching gel; IRL group - received one application of IRL (808 nm, 30 seconds, 3 J); Ble-IRL group - immediately after application of 35% H2O2, received an application of IRL, as described in the IRL group.. After 2 and 30 days (n = 10), the rats were euthanized and the jaws removed and processed for histological evaluation (H.E.) and immunohistochemistry. Form of analysis: Serial tissue sections with thickness of 5 µm stained in H.E. were evaluated by scores attributed to inflammation, and immunohistochemical analysis was performed by scores attributed to immunolabeling. The data were submitted to the Wilcoxon and Mann Whitney tests (P < 0.05). Results: At 2 days, there was a severe inflammation and the presence of necrosis in the occlusal and middle thirds of the pulp tissue in the Ble group, different compared to the Ble-IRL group with moderate to mild inflammation (P < 0.05). In the cervical third, there was moderate to severe inflammation in the Ble group, and mild in the Ble-IRL group (P < 0.05). At 30 days, there was absence of inflammation and bleached groups had an extensive deposition of tertiary dentin. Regarding IL-23, at 2 days was observed severe immunolabeling in the Ble group and moderate in the Ble-IRL group (P < 0.05); at 30 days, there was a reduction in IL-23 immunolabeling in the bleached groups, where Ble group had moderate immunolabeling, and Ble-IRL group had mild immunolabeling, without significant difference (P > 0.05). HIF-1α was more evident at 2 days in the Ble group, without significant difference with Ble-IRL (P > 0.05). The difference was observed between the bleached groups and their respective controls, which had no immunolabeling (P < 0.05); at 30 days, the Ble group had a reduction in HIF-1α immunolabeling, while the Ble-IRL group had an increase in immunolabeling from moderate to severe; however, the difference remained only between the bleached groups and their controls (P > 0.05). Conclusion: Infrared laser minimized the inflammatory infiltrate and IL-23 immunolabeling in the pulp tissue after dental bleaching, but did not influenced HIF-1α immunolabeling(AU)

Systemic Th17 response in the presence of periodontal inflammation

Abstract The relationship between periodontitis and the pathogenesis of other inflammatory diseases, such as diabetes, rheumatoid arthritis and obesity has been an important topic of study in recent decades. The Th17 pathway plays a significant role in how local inflammation can influence systemic inflammation in the absence of systemic pathology. Objective: To determine Th17 biased-cells in systemically healthy patients in the presence of generalized chronic periodontitis. Methodology: A total of 28 patients were recruited without systemic inflammatory pathology, which was determined by clinical history, the Health Assessment Questionnaire (HAQ) and rheumatoid factor detection. Of these patients, 13 were diagnosed as healthy/gingivitis (H/G) and 15 as generalized chronic periodontitis (GCP). Th17 (CD4+CD161+) cells and Th17IL23R+ (CD4+CD161+IL-23R+) cells were quantified by flow cytometry, based on the total cells and on the lymphocyte region, termed the "enriched population" (50,000 events for each). Results: The percentages of Th17 cells of the H/G and periodontitis groups were similar on total cells and enriched population (19 vs 21.8; p=4.134 and 19.6 vs 21.8; p=0.55). However, Th17IL23R+ cells differ significantly between periodontally healthy patients and generalized chronic periodontitis patients in both total cell (0.22% vs 0.65%; p=0.0004) and enriched populations (0.2% vs 0.75%; p=0.0266). Conclusions: GCP patients (otherwise systemically healthy) were characterized by increased Th17-proinflammatory cell phenotype positive for the IL-23 receptor in peripheral blood. The proportion of Th17 cells that are negative for the IL-23 receptor in the peripheral blood of systemically healthy patients seemed to be unaffected by the presence or absence of chronic periodontitis.

Analysis of the correlation between IL-23, IL-17and β-cell function in latent autoimmune diabetes in adult patients / 中国医师杂志

Objective To determine interleukin (IL)-23 and IL-17 level in latent autoimmune diabetes in adult (LADA) patients,and to explore the relationship of IL-23,IL-17and β-cell function in these patients.Methods Forty LADA patients from 2011 to 2016 in our hospital were selected as LADA group,and forty participants were as normal control group.Clinical and biochemical data was collected and the level of the IL-23 and IL-17 was measured with the enzyme linked immunosorbent assay (ELISA).The differences in interleukin levels among the two groups were compared.Pearson correlation analysis was used for investigating the relationship between the dependent of statistical significant interleukins and the independent data in the LADA patients,all closely related variables then were included in a stepwise multiple linear regression analysis.Results The levels of serum IL-23,IL-17 and IL-23/IL-17 were significantly higher in LADA group than those in control groups [3.54 (2.88 ～ 5.24) μg/L vs 1.98 (1.62 ～ 2.18) μg/L,P ＜0.05],[22.42 (17.71 ～ 26.07) ng/L vs 17.97 (17.15 ～ 20.70) ng/L,P ＜ 0.05],(175.79 ± 38.67 vs 105.22 ± 19.08,P ＜0.01).IL-23 and IL-17 in the LADA group were negatively correlated with fasting C peptide (FCP) (r =-0.42,r =-0.48,P ＜ 0.05),and the ratio of IL-23/IL-17 was positively correlated with fasting plasma glucose (FPG) (r =0.44,P =0.00).Stepwise multiple liner regression analysis showed that serum IL-23 and IL-17 level were independently associated with the FCP in LADA group.Conclusions IL-23 and IL-17 were possibly important proinflammatory factor in LADA patients,and can provide the new immunodiagnosis markers for LADA.

Protective effect of crocin in ulcerative colitis rats and its related mechanism / 中国组织工程研究

BACKGROUND: Crocin has anti-inflammatory and anti-oxidative stress effects. The therapeutic effects of crocin on ulcerative colitis and related mechanisms are still unclear. OBJECTIVE: To explore the protective effect of crocin in ulcerative colitis rats and its related mechanism. METHODS: Thirty Sprague-Dawley rats were randomly divided into five groups: normal group, model group, low-dose crocin group, high-dose crocin group, and positive control group. Experimental rat model of ulcerative colitis was induced by dextran sodium sulfate. Starting on the first day of modeling, rats were routinely fed in the normal group, were given sulfasalazine by gavage in the positive drug group, and were gavaged with 0.05 and 0.1 g/kg crocin in the low-and high-dose crocin groups, respectively. RESULTS AND CONCLUSION: One week after intervention, the crocin-treated rats had significantly decreased scores on colon tissue injury and Crohn’s disease activity index(P < 0.05). Compared with the model group, crocin groups had a decrease in the content of malondialdehyde and activity of myeloperoxidase(P < 0.05), and an increase in the activity of superoxide dismutase in the colon tissue(P < 0.05). Shown by immunohistochemical staining, compared with the model group, treatment with crocin significantly reduced immune responses of tumor necrosis factor α and interleukin 23 proteins after 1 week of intervention(P < 0.05). Compared with the model group, treatment with crocin downregulated the expression levels of total protein Bax, Caspase-3, Toll-like receptor 4 and MyD88(P < 0.05), and upregulated the expression of Bcl-2 in the intestinal tissue of rats(P < 0.05). These results indicate that crocin has a certain therapeutic effect in ulcerative colitis rats and its mechanism may be related to down-regulation of the Toll-like receptor 4/MyD88 signaling pathway and inhibition of oxidative stress, inflammation and apoptosis in the colon.

Analysis of the correlation between IL-23, IL-17and β-cell function in latent autoimmune diabetes in adult patients / 中国医师杂志

Objective@#To determine interleukin (IL)-23 and IL-17 level in latent autoimmune diabetes in adult (LADA) patients, and to explore the relationship of IL-23, IL-17and β-cell function in these patients.@*Methods@#Forty LADA patients from 2011 to 2016 in our hospital were selected as LADA group, and forty participants were as normal control group. Clinical and biochemical data was collected and the level of the IL-23 and IL-17 was measured with the enzyme linked immunosorbent assay (ELISA). The differences in interleukin levels among the two groups were compared. Pearson correlation analysis was used for investigating the relationship between the dependent of statistical significant interleukins and the independent data in the LADA patients, all closely related variables then were included in a stepwise multiple linear regression analysis.@*Results@#The levels of serum IL-23 , IL-17 and IL-23/IL-17 were significantly higher in LADA group than those in control groups [3.54(2.88~5.24)μg/L vs 1.98(1.62~2.18)μg/L, P<0.05], [22.42(17.71~26.07)ng/L vs 17.97(17.15~20.70)ng/L, P<0.05], (175.79±38.67 vs 105.22±19.08, P<0.01). IL-23 and IL-17 in the LADA group were negatively correlated with fasting C peptide (FCP) (r=-0.42, r=-0.48, P<0.05), and the ratio of IL-23/IL-17 was positively correlated with fasting plasma glucose (FPG) (r=0.44, P=0.00). Stepwise multiple liner regression analysis showed that serum IL-23 and IL-17 level were independently associated with the FCP in LADA group.@*Conclusions@#IL-23 and IL-17 were possibly important proinflammatory factor in LADA patients, and can provide the new immunodiagnosis markers for LADA.

Mechanism of Yupingfeng Granule on CU Rats Based on IL-23/IL-17 Inflammation Axis / 中国实验方剂学杂志

Objective::To study the effect of Yupingfeng granule on the degranulation of skin mast cells in chronic urticaria (CU) rats and the intervention mechanism of interleukin-23(IL-23), interleukin-17(IL-17) inflammation axis. Method::Totally 60 SPF SD rats were selected and randomly divided into normal group (normal saline), model group (normal saline), and loratadine group (0.9 mg·kg-1·d-1), high-dose Yupingfeng granules group (4.05 g·kg-1·d-1), middle-dose group (2.7 g·kg-1·d-1), low-dose group (1.35 g·kg-1·d-1). The CU rat model was reproduced through intraperitoneal injection of ovalbumin with aluminum hydroxide suspension and DTP vaccine. Histopathological changes of rat skin were observed by hematoxylin-eosin (HE) staining. Degranulation of mast cells in rat skin was determined by toluidine blue staining. IL-23 and IL-17 protein expressions in skin tissue were determined by immunohistochemistry (IHC). IL-23 and IL-17 mRNA transcription levels in skin tissue were determined by real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). Result::Yupingfeng granules can significantly alleviate the pathological manifestations of dermal edema, collagen beam distance, inflammatory cell infiltration of CU rats, and reduce the degranulation reaction of skin tissue mast cells in CU rats. The IL-23, IL-17 mRNA and protein expressions of the skin of model group were significantly increased compared with the normal group (P<0.05, P<0.01). Compared with the model group, Yupingfeng granules can significantly down-regulate IL-23 mRNA and protein expressions of CU rats (P<0.05, P<0.01). Yupingfeng granules had no significant regulatory effect on IL-17. Conclusion::Yupingfeng granule can significantly reduce the degranulation of mast cells in skin tissue of CU rats, and improve the pathological manifestations, such as dermal edema, serous exudation and inflammatory cell infiltration. The mechanism may be related to inhibiting the secretion of IL-23 pro-inflammatory cytokines and improving CU lesions.

Expression of interleukin-23 and interleukin-17 in the aqueous humor of patients with diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To investigate the correlation between the concentrations of interleukin-23(IL-23)and interleukin-17(IL-17)in the ocular aqueous humor(AH)at the different degrees of diabetic retinopathy(DR)patients. <p>METHODS: From June 2016 to June 2019, 70 patients(70 eyes)for age related cataract surgery were enrolled in Hubei Yichang Central People's Hospital. All cases were graded into 4 groups, includingⅠ group(20 cases): the control group(patients without diabetes), Ⅱ group(18 cases): diabetic patients without retinopathy, Ⅲ group(17 cases): diabetic patients with non-proliferative diabetic retinopathy, Ⅳ group(15 cases): diabetic patients with proliferative diabetic retinopathy. The levels of IL-23 and IL-17 in AH of the four groups were tested by Enzyme-linked immunosorbent assay(ELISA)and statistically analyzed by ANOVA respectively. The correlations between IL-17 and IL-23 were calculated by Person correction analysis.<p>RESULTS: The concentration of IL-23 in Ⅰgroup was low(22.18±5.48pg/mL),while those in Ⅱ(37.63±4.52pg/mL), Ⅲ(45.06±4.64pg/mL), Ⅳ(68.89±6.11pg/mL)groups respectively were higher. The IL-17 level inⅠ, Ⅱ, Ⅲ, Ⅳ groups were 4.69±2.03, 6.83±1.02, 9.52±1.30, 10.89±1.26pg/mL respectively. Comparison of IL-23 and IL-17 within four groups revealed: both were increased in Ⅱ group initially, and raised along with the progression of DR. According to the correlation analysis, the expression level of IL-17 of DM was typical positively correlated with IL-23.<p>CONCLUSION:The over-expression of IL-23 and IL-17 may have a synergistic effect on the occurrence and development, and the IL-23/IL-17 pathway might be associated with the severity of DR by aggravating the inflammatory response of retina. These results indicated that IL-23-IL-17 axis could be a new target for the early diagnosis and treatment of DR.

Tras los pasos de la interleucina-23. su papel en la psoriasis / Following the footsteps of interleukin - 23. its role in psoriasis

Resumen: La psoriasis es una enfermedad inflamatoria crónica multisistémica con compromiso de la piel, de distribución mundial, que afecta todas las edades y a ambos sexos; dentro de su complejo origen etiológico interactúan factores genéticos, inmunológicos y ambientales. Se ha descrito que la relación de la IL-23 y los linfocitos Th17 forman un eje que está íntimamente asociado con la patogénesis de esta enfermedad. La IL-23 es producida por macrófagos y células dendríticas. Está conformada por dos subunidades: la p40, que es común para la IL-12, y la p19, que es exclusiva de la IL-23. Dado que la subunidad p19 es abundante en la piel con psoriasis, se han venido diseñando moléculas que la bloquean, y que a la fecha han mostrado eficacia clínica en el control de las lesiones en la piel. En este artículo de revisión se presenta el panorama general de la IL-23 en psoriasis y el advenimiento de las moléculas dirigidas a modificar su actividad biológica.

Summary: Psoriasis is a multisystem chronic inflammatory disease with skin involvement, worldwide distribution that affects all ages and both sexes; Genetic, immunological and environmental factors interact within its complex etiological origin. It has been described that the relationship of IL-23 and Th17 lymphocytes form an axis that is intimately associated with the pathogenesis of this disease. IL-23 is produced by macrophages and dendritic cells and is composed of two subunits, p40 which is common for IL-12, and p19 that is unique to IL-23. Since p19 is abundant in the skin with psoriasis, molecules have been designed to block it, and to date they have shown clinical efficacy in the control of skin lesions. In this review article we present the general panorama of IL-23 in psoriasis and the advent of molecules aimed at modifying its biological activity.

Therapeutic Effect of Interleukin-23 p19 RNA Interference in Mice With Experimental Colitis / 胃肠病学

Background: Inflammatory bowel disease (IBD) is an autoimmune bowel disease with poor clinical outcome. Proinflammatory cytokines are the main targets of biological therapies. Interleukin-23 (IL-23) is a key factor in IBD pathogenesis. Monoclonal antibodies against subunit of IL-23 have been reported to have therapeutic effects. Aims: To investigate the therapeutic effect of IL-23 RNA interference in mice with experimental colitis and the underlying mechanism. Methods: 2,4,6-trinitrobenzenesulfonic acid (TNBS) enema was used to induce experimental colitis in mice, which were then injected with IL-23 p19 shRNA lentivirus or control shRNA lentivirus through caudal vein. Mice without lentivirus injection were served as model controls. After 2 weeks, disease activity index and histopathological inflammatory score, serum and colon tissue IL-23, IL-17 and tumor necrosis factor-α (TNF-α) expressions, as well as colon tissue Th17 cells were detected and compared. Results: IL-23 p19 shRNA therapy significantly reduced disease activity index and histopathological inflammatory score in mice with experimental colitis (P<0.05). By inhibiting IL-23 expression, IL-23 p19 shRNA suppressed further the colon tissue Th17 cells and subsequently reduced systemic and colon tissue IL-17 and TNF-α expressions significantly (P<0.05). Conclusions: IL-23 RNA interference has therapeutic effect in mice with experimental colitis. The mechanism lies in suppression of Th17 cells and its effector cytokine IL-17.

An association between single nucleotide polymorphisms of IL-23R gene and Keshan disease in Northwest Chinese Han population / 中华地方病学杂志

Objective To investigate the relationship between single nucleotide polymorphisms of interleukin 23 receptor (IL-23R) gene and Keshan disease (KD) in Northwest Chinese Han population.Methods A total of 285 Chinese Han subjects from Huangling,Shaanxi,including 79 KD patients (case group) and 206 control subjects (control group) were involved in this study.Genomic DNA was extracted from peripheral venous blood.The polymorphism of genetic variation was genotyped by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF).All sample groups were tested for Hardy-Weinberg equilibrium using goodness-of-fit x2 test.Differences in genotype distribution between two groups were compared by x2 test.Logistic regression analysis was applied to detect association using age as a confounding factor.Results The gene frequency distribution of IL-23R gene rs10889677 in case group and control group conformed to the Hardy-Weinberg equilibrium (x2 =0.254,P ＞ 0.05).Correlation analysis results:the difference of genotype frequency of IL-23R gene rs10889677 in case group (CC,CA,AA were 6.3％,36.7％,57.0％,respectively) and control group (CC,CA,AA were 5.3％,43.2％,51.5％,respectively) was not statistically significant (x2 =1.008,P ＞ 0.05).After age adjustment,there was no significant difference in genotype frequency of IL-23R gene rs10889677 (x2sdj =0.669,P ＞ 0.05) between two groups.Conclusion There is no correlation between IL-23R gene rs10889677 and KD in Northwest Chinese Han population.

Efficacy of desloratadine citrate disodium in the treatment of chronic urticaria and its effect on serum interleukin-23, interleukin-33 and PARC/CCL-18 / 中华皮肤科杂志

Objective To compare the efficacy of desloratadine citrate disodium versus loratadine in the treatment of chronic urticaria (CU),and to evaluate their effect on serum interleukin (IL)-23,IL-33 and pulmonary and activation-regulated chemokine/CC chemokine ligand 18 (PARC/CCL-18).Methods From January 2013 to December 2016,120 CU patients treated in Department of Dermatology,Wuwei Oncology Hospital were enrolled into this study,and divided into study group and control group by using a random number table.Patients in the study group took oral desloratadine citrate disodium tablets 8.8 mg once a day,and patients in the control group took loratadine tablets 10 mg once a day.The treatment lasted 28 days.The therapeutic effect was compared between the two groups,and changes in serum levels of IL-23,IL-33 and PARC/CCL-18 were compared before and after treatment.Statistical analysis was carried out by using two-sample t test and chi-square test for comparing indices between the two groups.Results The response rate was significantly higher in the study group (88.33％,53/60) than in the control group (61.67％ [37/60],x2 =15.352,P ＜ 0.01).After the treatment,the serum levels of IL-23,IL-33 and PARC/CCL-18 in the study group significantly decreased to 87.72 ± 22.16 ng/L,95.94 ± 18.27 ng/L,85.93 ±27.34 μg/L respectively,which were all lower than those in the control group (104.21 ± 32.05 ng/L,106.27 ±20.93 ng/L,95.72 ± 30.28 μg/L,respectively;t =3.264,4.034,3.934,respectively,P =0.020,0.006,0.015,respectively).No significant difference was observed in the incidence of adverse reactions between the study group and control group (P =0.298).Conclusion Desloratadine citrate disodium can markedly improve the clinical symptoms of CU with favorable safety,likely by inhibiting the immune response of the body and reducing the effect of chemokines on the chemotaxis of inflammatory cells.

Recent medical therapy for psoriasis

Psoriasis is a chronic inflammatory disease. Medical therapy is the mainstay of the management of psoriasis, and the main target of psoriasis treatment is immunological dysregulation. Cyclosporine and methotrexate, the main conventional psoriasis treatments, usually lead to a Psoriasis Area and Severity Index (PASI) 75 response in 50% to 60% of patients, but show some organ toxicity. Biologics for psoriasis have recently become the main therapeutic agents for moderate to severe psoriasis unresponsive to conventional treatment. Tumor necrosis factor-α inhibitors were the first anti-psoriatic biologics to be developed, and also show good efficacy for psoriatic arthritis. Ustekinumab, the sole biologic designed for the inhibition of interleukin (IL)-12/23, has been most widely used for psoriasis in Korea. The main strength of ustekinumab is its relatively long treatment interval. IL-17 inhibitors have recently been introduced in Korea for psoriasis treatment. Secukinumab and ixekizumab are currently available IL-17 inhibitors that block the development of psoriasis lesions in the downstream events of psoriasis pathogenesis. They have excellent therapeutic efficacy, with a PASI 90 response in up to 60%–70% of patients. Selective IL-23 inhibitors have been more recently introduced in our country. They have an excellent PASI 90 response, and a longer injection interval than IL-17 inhibitors. New immunological modulators such as phosphodiesterase inhibitors, tyrosine kinase 2 inhibitors, and janus kinase inhibitors are planned to be introduced for psoriasis treatment. These are small molecules that can be administered orally, and some patients who are reluctant to receive injection therapy are expected to favor these therapeutic agents.