Correlation of Blood and Intestinal Mucosa miR-34a Expressions with Disease Severity in Ulcerative Colitis Patients.

BACKGROUND: miR-34a has been implicated in many autoimmune diseases and gastrointestinal diseases. However, the expression of miR-34 in ulcerative colitis (UC) patients were not fully studied. This study was performed to in-vestigate the association of blood and intestinal tissue miR-34a expression of patients with disease severity in UC patients. METHODS: Our study enrolled 82 patients with UC and 80 age- and gender- matched healthy individuals. Blood miR-34a expressions were detected using reverse transcription-polymerase chain reaction (RT-PCR). Local intestinal miR-34a, STAT3 mRNA and IL-23 mRNA expressions were also detected in the lesioned area and adjacent non-affected intestinal tissue in patients. Disease severity of UC was assessed by Mayo score. The diagnostic value of both blood and local miR-34a expression for UC patients was assessed by receiver operating characteristic (ROC) curve. RESULTS: Blood miR-34a was increased in UC patients in contrast with healthy individuals with statistical significance. In UC patients, local intestinal miR-34a expressions were markedly upregulated compared to adjacent non-affected intestinal tissue. Local intestinal miR-34a expressions were positively correlated with STAT3 mRNA and IL-23 mNRA. Both blood and local miR-34a expressions were significantly and positively related to Mayo scores. ROC curve analysis indicated that both blood and local miR-34a expressions may act as decent marker for Mayo grade. CONCLUSIONS: Blood and intestinal tissue miR-34a expressions are correlated with disease severity in UC patients. Both blood and intestinal tissue miR-34a expressions may serve as potential diagnostic and prognostic makers for UC. Therapeutic methods targeting miR-34a may act as potential ways for UC treatment.

Serum Levels of Interleukins in Endometriosis Patients: A Systematic Review and Meta-analysis.

OBJECTIVE: The aims of this systematic review and meta-analysis were to produce a comprehensive survey of the serum levels of interleukins (ILs) in untreated people with endometriosis compared with people without endometriosis. DATA SOURCES: A systematic literature search of English language studies within Cinahl, Medline Complete, PubMed, and Scopus from inception to May 2023 was performed. METHODS OF STUDY SELECTION: We included studies that compared IL serum levels in people with endometriosis to those without endometriosis. Meta-analysis was performed on IL-1RA, IL-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IL-18, IL-23, and IL-37. TABULATION, INTEGRATION, AND RESULTS: The systematic search retrieved 651 studies, of which 77 underwent a full-text review. A total of 30 studies met inclusion criteria for the meta-analysis. IL-1Ra, IL-6, and IL-37 serum levels were 2.56 (95% CI 2.20-2.92, p <.001), 1.38 (95% CI 0.58-2.17, p <.001), and 1.77 (95% CI 1.33-2.20, p <.001) standard deviations higher in the patients with endometriosis compared with patients without endometriosis while IL-23 serum levels 0.40 (95% CI -0.73 to -0.07, p = .02) standard deviations lower, respectively. CONCLUSION: There is mounting evidence that ILs, especially IL-6, may be good candidates for unique noninvasive diagnostic tools and/or treatment pathways for endometriosis.

Modulation of Interleukin-23 Signaling With Guselkumab in Biologic-Naive Patients Versus Tumor Necrosis Factor Inhibitor-Inadequate Responders With Active Psoriatic Arthritis.

OBJECTIVE: We assessed and compared immunologic differences and associations with clinical response to guselkumab, a fully human interleukin (IL)-23p19 subunit inhibitor, in participants with active psoriatic arthritis (PsA) who were biologic-naive or had inadequate response to tumor necrosis factor inhibitors (TNFi-IR). METHODS: Serum biomarker levels at baseline and after treatment with guselkumab 100 mg every 8 weeks were compared between biologic-naive (n = 251) and TNFi-IR (n = 93) subgroups identified in the pooled DISCOVER-1/DISCOVER-2/COSMOS data set. Baseline biomarker levels determined by achievement of week 24 clinical responses (≥75%/90% improvement in Psoriasis Area and Severity Index [PASI 75/90], Investigator's Global Assessment [IGA] of psoriasis score 0/1 and ≥2-point improvement], ≥20% improvement in American College of Rheumatology criteria [ACR20]) were compared between prior treatment subgroups. RESULTS: Baseline IL-22, TNFα, and beta defensin-2 (BD-2) levels were significantly lower in biologic-naive than in TNFi-IR participants. With guselkumab, week 24 IL-17A, IL-17F, IL-22, serum amyloid A, C-reactive protein, IL-6, and BD-2 levels were significantly reduced from baseline in biologic-naive and TNFi-IR participants (≥1.4-fold difference, nominal P < 0.05). Clinical responders to guselkumab exhibited significantly higher baseline levels of several biomarkers than nonresponders (IL-17A, IL-17F, BD-2 in biologic-naive PASI 90 responders; IL-17A, BD-2 in TNFi-IR IGA 0/1 responders; IL-22, BD-2 in TNFi-IR PASI 90 responders [nominal P < 0.05]) and trended higher in TNFi-IR ACR20 responders. CONCLUSION: Guselkumab modulates IL-23 signaling and provides consistent pharmacodynamic effects in both biologic-naive and TNFi-IR PsA patients. Significantly elevated baseline IL-22, TNFα, and BD-2 levels and associations between baseline IL-22, IL-17A, and BD-2 levels and skin responses to guselkumab suggest greater dysregulation of IL-23/Th17 signaling in patients with TNFi-IR.

Value of IL-1ß and IL-23 in Predicting 28-Day Mortality Due to Sepsis: A Retrospective Study.

BACKGROUND This research aimed to explore the utility of Interleukin-1ß (IL-1ß) and IL-23 as potential biomarkers for the diagnosis and prognosis of sepsis. MATERIAL AND METHODS This study included 74 adult individuals with sepsis, 45 ICU controls, and 50 healthy individuals attending routine physical examinations. IL-1ß and IL-23 levels were assessed and analyzed on the admission day. Univariate Cox regression analyses were utilized to explore the association of IL-1ß and IL-23 with sepsis survival. Furthermore, receiver operating characteristic (ROC) analysis was employed to evaluate the value of IL-1ß and IL-23 to predict 28-day mortality due to sepsis. RESULTS Serum concentrations of IL-1ß and IL-23 were significantly higher in septic patients relative to healthy and ICU controls (P<0.001). IL-1ß and IL-23 levels in non-survivors were significantly higher than in survivors (P<0.001). IL-1ß (hazard ratio; HR=1.06, P<0.001) and IL-23 (HR=1.02, P=0.031) were independent risk variables for 28-day mortality in sepsis patients, which were strongly associated with the severity of sepsis. The area under the ROC curve for predicting 28-day fatality in sepsis was 0.66 for IL-1ß (P=0.024, 95% confidence interval; CI: 0.54-0.76) and 0.77 for IL-23 (P<0.001, 95% CI: 0.65-0.86). Furthermore, compared with low serum IL-1ß (<9.41 pg/mL) and IL-23 (<6.77 pg/mL) levels, septic patients with high serum IL-1ß (≥9.41 pg/mL) and IL-23 (≥6.77 pg/mL) levels had poorer survival. CONCLUSIONS Serum IL-1ß and IL-23 values were higher in patients with sepsis and are potential diagnostic and prognostic markers for sepsis, but this needs to be confirmed by prospective studies.

An optical system for noninvasive microscopy of psoriatic mice in vivo.

Psoriasis is a chronic inflammatory skin disease involved with both complex morphological changes of skin and immune processes. The clinical diagnostics and research of psoriasis often require invasive biopsy which lacks their real-time dynamics in vivo. Here we report a noninvasive microscopic system developed by combining in vivo fluorescent microscopy, optical clearing, and immunolabeling to enable real-time imaging of immune cells and cytokines in blood flow in psoriatic animal models. The vascular morphology and time-lapse kinetics of interleukin (IL)-23, IL-17, tumor necrosis factor-α, and CD4+ cells in blood are captured at submicron resolution through the thickening epidermis and opaque scales during the development of psoriasis in vivo. Our data suggest IL-23 recruits CD4+ cells to release IL-17 in blood that further leaks out in the psoriatic skin area. This optical system enables noninvasive and real-time assessment of immune molecules and cells in vivo, providing good potential for medical researches on psoriasis.

Plasma interleukin-23 and circulating IL-17A+IFNγ+ ex-Th17 cells predict opposing outcomes of anti-TNF therapy in rheumatoid arthritis.

OBJECTIVES: TNF-α inhibitors are widely used in rheumatoid arthritis (RA) with varying success. Response to TNF-α inhibition may reflect the evolution of rheumatoid inflammation through fluctuating stages of TNF-α dependence. Our aim was to assess plasma concentrations of Th-17-related cytokines and the presence of circulating effector T-cells to identify predictors of response to TNF-α inhibitors. METHODS: Ninety-three people with RA were seen prior to and 4-6 months after commencing etanercept or adalimumab. Plasma concentrations of Th17-related cytokines, circulating effector T-cells, their production of relevant transcription factors and intracellular cytokines were measured at baseline. EULAR response criteria were used to define poor (ΔDAS28 ≤ 1.2 and/or DAS28 > 3.2) and good (ΔDAS28 > 1.2 and DAS28 ≤ 3.2) responders. Multivariate logistic regression was used to identify predictors of response. RESULTS: Participants with plasma IL-23 present at baseline were more likely to be poor responders [15/20 (75%) of IL-23+ versus 36/73 (49.3%) of IL-23-; p = 0.041]. While frequencies of Th1, Th17, ex-Th17 and Treg cell populations were similar between good and poor responders to anti-TNF therapy, IL-17A+IFNγ+ ex-Th17 cells were more prevalent in good responders (0.83% of ex-TH17 cells) compared to poor responders (0.24% of ex-Th17 cells), p = 0.023. Both plasma IL-23 cytokine status (OR = 0.17 (95% CI 0.04-0.73)) and IL-17A+IFNγ+ ex-Th17 cell frequency (OR = 1.64 (95% CI 1.06 to 2.54)) were independently associated with a good response to anti-TNF therapy. Receiver operator characteristic (ROC) analysis, including both parameters, demonstrated an area under the ROC curve (AUC) of 0.70 (95% CI 0.60-0.82; p = 0.001). CONCLUSIONS: Plasma IL-23 and circulating IL-17A+IFNγ+ ex-Th17 cells are independently associated with response to anti-TNF therapy. In combination, plasma IL-23 and circulating IL-17A+IFNγ+ ex-Th17 cells provide additive value to the prediction of response to anti-TNF therapy in RA.

Regression of Triple-Negative Breast Cancer in a Patient-Derived Xenograft Mouse Model by Monoclonal Antibodies against IL-12 p40 Monomer.

Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor ß (TGFß) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.

IL-23R Variant rs11805303 Is Associated With Susceptibility to the Development of Cutaneous Leishmaniasis in Leishmania guyanensis-Infected Individuals.

BACKGROUND: Emerging evidence suggests that the interleukin (IL) 17/ IL-23 axis may play a role in the pathogenesis of leishmaniasis. Our aim was to investigate whether the IL-23R variant rs11805303 is a risk factor for the development of cutaneous leishmaniasis (CL) in Leishmania guyanensis-infected individuals. METHODS: We genotyped by polymerase chain reaction-restriction fragment length polymorphism the rs11805303 C/T in 828 patients with CL and 806 healthy individuals. Plasma tumor necrosis factor-α, IL-6, interferon-γ, IL-1ß, and IL-17 were measured with the Bioplex assay. RESULTS: The distribution of the genotypes differed between patients with CL and healthy controls with a common odds ratio of 1.78 (P = 2.2 × 10-11) for the disease-associated T allele. Leishmania guyanensis-infected individuals homozygous for the T allele show a 200% increased risk of progressing to disease development, with a 95% confidence interval ranging from 81% to 400% (P = 9.9 × 10-6) in comparison to individuals homozygous for the C allele. Males homozygous for the T allele have higher plasma levels of IL-17 compared with heterozygous or homozygous CC individuals. CONCLUSIONS: The present association of the IL-23R variant rs11805303 with the development of CL suggests that the IL-17/IL-23 axis may play an important role in the pathogenesis of CL.

The abnormal level of HSP70 is related to Treg/Th17 imbalance in PCOS patients.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a disease with chronic nonspecific low-grade inflammation. The imbalance of immune cells exists in PCOS. Several studies have found that heat shock protein 70 (HSP70) may be involved in the immunological pathogenesis of PCOS, but the relationship between HSP70 and Regulatory T cell (Treg)/T helper cell 17(Th17) ratio remains unclear. This study aims to explore the correlation between HSP70 and Treg/Th17 ratio and to provide evidence for the role of HSP70 in the immunological etiology of PCOS. RESULTS: There was no significant difference in age and body mass index (BMI) between the two groups. The concentrations of basal estradiol (E2), basal follicle-stimulating hormone (FSH) did not show a significant difference between the two groups. The concentrations of basal luteinizing hormone (LH) (P < 0.01), testosterone (T) (P < 0.01), glucose (P < 0.001) and insulin (P < 0.001) in PCOS patients were significantly higher than those in the control group. The protein levels of HSP70 were significantly higher in serum in the PCOS group (P < 0.001). The percentage of Treg cells was significantly lower (P < 0.01), while the percentage of the Th17 cells of the PCOS group was significantly higher than that of the control group (P < 0.05). The ratio of Treg/Th17 in the PCOS group was significantly lower (P < 0.001). The concentrations of Interleukin (IL)-6, IL-17, and IL-23 were significantly higher, while the levels of IL-10 and Transforming growth factor-ß (TGF-ß) were significantly lower in the PCOS group (P < 0.001). Spearman rank correlation analysis showed a strong negative correlation of serum HSP70 levels with Treg/Th17 ratio, IL-10, and TGF-ß levels. In contrast, HSP70 levels were significantly positively correlated with IL-6, IL-17, IL-23, LH, insulin, and glucose levels. CONCLUSION: The abnormal level of HSP70 is correlated with Treg/Th17 imbalance and corresponding cytokines, which indicates that HSP70 may play an important role in PCOS immunologic pathogenesis.

Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients.

The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.

IL-23 and IL-17 in acute ischemic stroke: Correlation with stroke scales and prognostic value.

BACKGROUND AND PURPOSE: Inflammation plays a crucial role in brain damage following stroke. Here, we evaluate interleukin 23 (IL-23) and interleukin 17 (IL-17) in the inflammatory process and its relations with neurological findings of patients with acute ischemic stroke (AIS). MATERIAL AND METHODS: Fifty consecutive patients with AIS admitted to our hospital within 24 h of stroke onset were enrolled in a prospective cohort study. Serum IL-23 and IL-17 were measured in the first, third and fifth day after the stroke. Neurological stroke severity were determined with the National Institutes of Health Stroke Scale (NIHSS) and with the modified Rankin Scale (mRS) within 24 h of the acute event, on the third and fifth day after the stroke, and at the time of hospital discharge. RESULTS: Both neurological scores for stroke outcome at hospital discharge were related to IL-23 protein within 24 h and on the fifth day, but with low stroke outcome predictive values. The other measurements did not show predictive capacity for stroke outcome. There was a significant increase in median serum concentrations of IL-23 on the fifth day (p < 0.001) and in IL-17 median levels on the third day compared to the first 24 h after the acute injury (p < 0.001). However, there was no correlation between IL-23 and IL-17 levels with neurological outcomes at hospital discharge or after four years. CONCLUSION: IL-23 and IL-17 increase after stroke, but had no sufficient discriminative capacity to be of clinical use as outcome stroke predictors.

IL-23/Th17 pathway and IL-17A gene polymorphism in Egyptian children with immune thrombocbytopenic purpura.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an acquired complex autoimmune thrombocytopenia. Uncontrolled cellular immune response is one of the key triggers for the loss of immune tolerance in ITP patients. The purpose of this study was to investigate the association of IL-23/Th17, IL-17A and IL-17A rs2275913 gene polymorphism with ITP in Egyptian children. METHODS: 60 patients with ITP and 50 healthy control children from Minia city- Egypt were involved. Serum levels of IL-23 and IL-17A were determined by enzyme-linked immunosorbent assay. The frequency of Th17 cells was measured using flow cytometer. Genotyping for IL-17A was performed via polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Comparing children with ITP to controls, serum levels of IL-23 and IL-17A as well as Th17 cells percentage were significantly increased (p <  0.001). Also, higher levels of these ILs and Th17 cells percentage were associated with decreased platelet count within ITP patients (p <  0.001). Analysis of genotype frequencies for IL-17A rs2275913 polymorphism and its alleles (A, G) showed no significant difference between cases and controls. Likewise, no significant differences were demonstrated between acute and chronic ITP regarding both IL-17A rs2275913 polymorphism prevalence and levels of IL-23, IL-17A plus Th17 cells percentage. The frequency of A alleles was 85 and 86% within patients and controls, respectively. CONCLUSIONS: Elevated levels of IL-23, IL-17A and Th17 cells may be involved in ITP pathogenesis while IL-17A polymorphism rs2275913 is not prevalent in Egyptian children with ITP.

Low IL-23 levels in peripheral blood and bone marrow at diagnosis of acute leukemia in children increased with the elimination of leukemic burden.

IL-23 is an IL-12 cytokine family member with pleiotropic functions that regulates tumour growth in various cancer types, exhibiting both anti-tumorigenic and pro-tumorigenic properties. Preclinical studies have shown a potential anti-leukemic action on childhood B-ALL cells. The study involved 65 children with acute leukemia [59 patients with acute lymphoblastic leukemia (ALL) and 6 patients with acute myeloid leukemia (AML)] and 27 healthy controls. Using an enzyme-linked immunosorbent assay, we aimed to determine the IL-23 levels in the peripheral blood (PB) and bone marrow (BM) of patients at diagnosis and at the end of the induction therapy (EIT). PB IL-23 levels were lower in leukemia patients compared to the healthy controls. In all acute leukemia patients, IL-23 levels were significantly lower at diagnosis both in PB (P = .015) and in BM (P = .037) compared to the PB and BM concentrations at the EIT. The same pattern was present in both subgroups of ALL and AML patients. The high leukemic burden at diagnosis was related with lower IL-23 levels, which were increased with the disease remission. Considering the anti-leukemic potential of this cytokine, the elevation of the IL-23 concentration at the disease remission indicates a beneficial role of IL-23 in paediatric acute leukemia.

Association of interleukin-2, interleukin-21 and interleukin-23 with hyperlipidemia in pediatric type 1 diabetes.

BACKGROUND: In type 1 diabetes mellitus (T1DM), cytokines have a central role in orchestrating multicellular relations between ß-cells and immune cells. This study aims to investigate the role of interleukin (IL)-21, IL-23, and IL-2, and their association with dyslipidemia in T1DM children. METHODS: The sample population consisted of 30 healthy controls and 70 children with T1DM, the latter of which were split into two groups according to the duration of their T1DM diagnosis: recent (≤ 1 year; n = 21) and older (> 1 year; n = 49) diagnoses. RESULTS: Fasting blood sugar and glycated hemoglobin levels in all diabetic children were significantly (P < 0.001) higher, whereas levels of plasma C-peptide were markedly (P < 0.001) lower in children with T1DM compared to healthy controls. In older T1DM diagnosis children, the levels of creatinine were noticeably (P < 0.05) increased relative to healthy controls. In all diabetic children, levels of total triglyceride, cholesterol, and low-density lipoprotein were increased significantly (P < 0.001) than those of healthy controls. Furthermore, the IL-21 and IL-23 mRNA expressions of all children with T1DM were elevated significantly (P < 0.001) relative to healthy controls, whereas IL-2 levels revealed a significant (P < 0.001) decrease in all diabetic children. CONCLUSION: There was a synergistic interplay between IL-21 and IL-23 with an antagonistic action of IL-2 in T1DM patients, and all three interleukins were associated with dyslipidemia in diabetic children. Importantly, therapies targeting IL-21 and IL-23 are promising targets for preventive strategies against the development of T1DM and its complications.

Expression levels of IL-17/IL-23 cytokine-targeting microRNAs 20, 21, 26, 155, and Let-7 in patients with relapsing-remitting multiple sclerosis.

OBJECTIVE: Although multiple sclerosis (MS) is known to be an immune-mediated disease, very little is known about its etiopathogenesis. MicroRNAs (miRNAs) are small non-coding proteins involved in the regulation of gene expression. T-cell activation potential in neurodegenerative diseases has been a research topic of interest in recent years Cytokines play an important role in the course and pathogenesis of MS, The aim of the present study was to analyze expression levels of miR-20, miR-21, miR-26, miR-155, and Let-7, which target the cytokines interleukin IL-17 and IL-23, in order to evaluate the relationship between MS and miRNAs that modulate the expression of cytokines involved in the autoimmune pathway.MATERIALS and METHODS: The study included 20 relapsing-remitting multiple sclerosis (MS) patients who were at least 18 years of age and were undergoing outpatient immunomodulatory therapy and 20 healthy, unrelated individuals who had no systemic disease and were not taking any medication as a control group. Peripheral blood samples were collected from all participants into EDTA-containing tubes and plasma was isolated for cDNA synthesis. From these cDNA samples, miRNA expression levels were quantitatively analyzed via melting curve analysis using the miScript SYBR Green kit in a Rotor-Gene Q real-time PCR device. RESULTS: Comparison of miRNA expression levels in the peripheral blood samples and MS patients and healthy subjects revealed that the MS patients had significant upregulation of miR-20 and downregulation of miR-26 and miR-155 compared to the control group (p<0.005).CONCLUSION: Dysregulation of miRNA expression may play a role in the pathogenesis of MS.

Serum high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin (IL)-1ß, IL-17A and IL-23 levels in patients with hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, recurrent inflammatory skin disease that leads to scar formation. The immune pathogenesis of HS is not fully understood and inhibitors of tumor necrosis factor (TNF)-α, interleukin (IL)-17, IL-1, IL-23 can be used for treating HS. Identification of serum biomarkers may help understanding individual differences in HS pathogenesis, evaluating disease severity and developing more effective treatment methods. OBJECTIVES: To assess the serum levels of proinflammatory cytokines TNF-α, IL-1ß, IL-17A, IL-23 and high-sensitivity C-reactive protein (hs-CRP) in patients with HS and to evaluate the impact of treatment on cytokine levels. METHODS: Serum proinflammatory cytokine and hs-CRP levels were measured using enzyme-linked immunosorbent assay kits in 24 healthy controls and in 26 HS patients at baseline and after a 3-month treatment. Patients were treated with clindamycin, adalimumab, dapsone, doxycycline and acitretin, based on HS condition and laboratory results. Control, pre-treatment and post-treatment values were compared. RESULTS: HS patients had significantly higher hs-CRP levels than controls which decreased following treatment (p = 0,010, p = 0,007). No significant difference was found in serum levels of TNF-α, IL-1ß, IL-17A, IL-23 compared to controls and post-treatment levels. CONCLUSIONS: There is insufficient data to suggest TNF-α, IL-1ß, IL-17A and IL-23 as serum biomarkers in HS. hs-CRP can be used as an indicator of treatment response and systemic inflammation.

The roles played by IL-10, IL-23 and IL-17A in term delivery.

BACKGROUND: The immune system significantly participates in the development of the successful delivery process. The roles played by cytokine molecules in the induction of term delivery are yet to be clarified. The aim of this project was to explore the serum levels of interleukin-10 (IL-10), IL-17A, and IL-23 in the mothers with term and prolonged pregnancy and their infants. MATERIALS AND METHODS: In this study, 60 samples were collected from either mothers with term and prolonged pregnancy or their infants, collectively 240 samples. Serum levels of IL-10, IL-17A and IL-23 were explored using enzyme linked immunosorbent assay (ELISA) technique. RESULTS: IL-10 serum levels significantly decreased in the neonates with prolonged pregnancy when compared to their mothers. Serum levels of IL-23 were increased either in term or prolonged pregnancy neonates when compared to their corresponded mothers. Serum levels of IL-10 and IL-23 significantly decreased and increased, respectively, in the female in comparison to male in the prolonged pregnancy neonates. IL-10 also significantly decreased in the term mothers who had higher gravidity. CONCLUSION: Although, IL-17A does not play a key role in the delivery mechanism, IL-10 and IL-23 may be considered as potential factors in the modulation of term delivery.

Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity.

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP-1, IL-8, IL-18 and IL-23 levels have a strong correlation with HS (P < .010-0.004; AUC = 0.790-0.883). Notably, combinations of two or three cytokines (TNF-a, MCP-1 and IL-23; AUC: 0.942, Nagelkerke R2 : 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.

Pulmonary function severity in relation to interleukin-23 levels in patients with psoriasis vulgaris.

Background Interleukin-23 (IL-23), a key inflammatory regulator in the pathogenesis of psoriasis, is suspected to play a role in the onset of pulmonary dysfunction (chronic obstructive pulmonary disease) in psoriasis. Despite that, pulmonary function tests are rarely studied in these subjects. This study aims to seek a possible relation between pulmonary function in psoriasis patients serum IL-23. Methods For this analytical cross-sectional study, male psoriasis patients in the age group of 25-45 years were recruited from dermatology out patient department (n = 40). Age and BMI matched apparently healthy individuals were recruited as control group (n = 40). After obtaining demographic and personal details, anthropometric parameters and blood pressure were recorded. The severity of psoriasis was assessed using Psoriasis Area and Severity Index score. Pulmonary function was assessed using computerized spirometry, and serum IL-23 was measured using ELISA. Results Forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow rate, and forced expiratory flow at 25%-75% of the pulmonary volume (FEF25%-75%) were significantly reduced in psoriasis. Based on the percentage of predicted values FEF25%-75% was significantly reduced in psoriasis. Serum IL-23 (pg/mL) was significantly higher in psoriasis. The increase in IL-23 in psoriasis subjects does not correlate with their pulmonary function. Conclusions Psoriasis may be associated with a reduced lung function even when the disease is in the mild stage. Increased IL-23 found in these subjects is suggestive of systemic inflammation, which indirectly lowers lung function.