Serum IL-18 Levels Research Articles

Honokiol suppresses the aberrant interactions between renal resident macrophages and tubular epithelial cells in lupus nephritis through the NLRP3/IL-33/ST2 axis

Lupus nephritis (LN) is a type of immune-complex nephritis caused by systemic lupus erythematosus and is a major contributor to mortality and morbidity. Honokiol (HNK) has been found to have a therapeutic effect on LN, but its action mechanism remains unclear. In this study, we first demonstrated that HNK attenuates kidney injury in MRL/lpr mice. Results from RNA sequencing combined with ingenuity pathway analysis suggested that HNK plays an anti-LN role through inhibition of the NLRP3 inflammasome and IL33. GEO chip data, single-cell data, and clinical samples from LN patients demonstrated that the pyroptosis and IL-33/ST2 pathways are abnormally activated during the stage of LN. In vivo, similar to the results of the AAV-mediated NLRP3 shRNA MRL/lpr model, HNK downregulated serum and renal IL-33 levels, and suppressed NLRP3 inflammasome and the IL-33/ST2 axis in the kidney. In vitro, co-culturing NLRP3-overexpressing or IL-33 knocked-down rat renal macrophages with NRK-52E cells confirmed that NLRP3 activation in resident macrophages directly upregulates IL-33, which in turn mediates the IL-33/ST2/NF-κB pathway to promote the inflammatory response of renal tubular epithelial cells. Furthermore, a molecular docking model and surface plasmon resonance analysis were utilized to demonstrate a direct interaction between HNK and NLRP3. In conclusion, this study provides a novel anti-LN treatment strategy in which HNK plays a preventive and therapeutic role against LN by suppressing the abnormal crosstalk between renal resident macrophages and renal tubular epithelial cells by inhibiting the activation of the NLRP3/IL-33/ST2 axis.

CXCL12 and CXCR4 as Novel Biomarkers in Uric Acid-Induced Inflammation and Patients with Gouty Arthritis.

The aim of this study was to evaluate the expression of chemokine receptor CXCR4 and its ligand CXCL12 in patients with gout and uric acid-induced inflammation. A total of 40 patients with intercritical gout and 27 controls were consecutively enrolled. The serum levels of interleukin-1β (IL-1β), IL-18, CXCL12, and CXCR4 were assessed using an enzyme-linked immunosorbent assay. The gene and protein expressions for these target molecules were measured in human U937 cells incubated with monosodium urate (MSU) crystals using a real-time reverse transcription polymerase chain reaction and Western blot analysis. Patients with intercritical gout showed higher serum IL-1β, IL-18, and CXCL12 levels, but not the serum CXCR4 level, than in the controls.The serum CXCR4 level in gout patients was associated with the serum IL-18 level, uric acid level, and uric acid/creatinine ratio (r = 0.331, p = 0.037; r = 0.346, p = 0.028; and r = 0.361, p = 0.022, respectively). U937 cells treated with MSU crystals significantly induced the CXCL12 and CXCR4 mRNA and protein expression in addition to IL-1β and IL-18. In cells transfected with IL-1β siRNA or IL-18 siRNA, the CXCL12 and CXCR4 expression was downregulated compared with the non-transfected cells in MSU crystal-induced inflammation. In this study, we revealed that CXCL12 and CXCR4 were involved in the pathogenesis of uric acid-induced inflammation and gouty arthritis.

Interleukin-39 is a novel cytokine associated with type 2 diabetes mellitus and positively correlated with body mass index.

It is suggested that cytokines play a key role in the pathogenesis of type 2 diabetes mellitus (T2DM). Therefore, this study explored two recently discovered cytokines, interleukin (IL)-37 (anti-inflammatory) and IL-39 (pro-inflammatory), in T2DM due to limited data in this context. Serum IL-37 and IL-39 levels were determined in 106 T2DM patients and 109 controls using enzyme-linked immunosorbent assay kits. Serum levels (median and interquartile range) of IL-37 (79 [47-102] vs. 60 [46-89] ng/L; probability [p]=.04) and IL-39 (66 [59-69] vs. 31 [19-42] ng/L; p< .001) were significantly elevated in T2DM patients compared to controls. As indicated by the area under the curve (AUC), IL-39 (AUC=0.973; p< .001) was more predictable for T2DM than IL-37 (AUC=0.582; p= .039). Elevated levels of IL-39 were significantly associated with T2DM (odds ratio=1.30; p< .001), while IL-37 did not show this association. Classification of IL-37 and IL-39 levels by demographic and clinical characteristics of patients revealed some significant differences including gender (IL-39), body mass index (BMI; IL-37 and IL-39) and diabetic neuropathy (IL-39). BMI was positively correlated with IL-39 (correlation coefficient [rs ]=0.27; p= .005) and glycosylated haemoglobin (rs = 0.31; p= .001), and negatively correlated with age at onset (rs = -0.24; p= .015). IL-37 and IL-39 levels were elevated in the serum of T2DM patients. Besides, IL-39 is proposed to be a novel cytokine associated with T2DM and positively correlated with BMI.

Anti-tumor necrosis factor alpha treatment does not influence serum levels of the markers associated with radiographic progression in ankylosing spondylitis.

The study aimed to determine the levels of change of the markers related to radiographic progression, such as Dickkopf-1 (DKK-1), sclerostin (SOST), bone morphogenetic protein (BMP)-2 and -4, and interleukin (IL)-17 and -23, in ankylosing spondyloarthritis (AS) during anti-tumor necrosis factor alpha (TNF-α) treatment. Fifty-three anti-TNF-α naïve AS patients (34 males, 19 females; median: 38 years; range, 20 to 52 years) refractory to conventional treatments meeting the modified New York criteria or Assessment of SpondyloArthritis International Society classification criteria were enrolled to this cross-sectional, controlled study between October 2015 and January 2017. Fifty healthy volunteers (35 males, 15 females; median: 36 years; range, 18 to 55 years) with similar age and sex characteristics were recruited. Serum DKK-1, BMP-2, BMP-4, SOST, IL-17, and IL-23 levels were measured in both groups. The serum levels of the markers were measured again after about two years (mean follow-up duration of 21.7±6.4 months) in AS patients who started anti-TNF-α treatment. Demographic, clinical characteristics, and laboratory parameters were recorded. The disease activity at the time of inclusion was assessed through the Bath Ankylosing Spondylitis Disease Activity Index. Serum DKK-1, SOST, IL-17, and IL-23 levels in the AS group before anti-TNF-a treatment were significantly higher compared to the control group (p<0.01 for DKK-1, p<0.001 for others). There was no difference regarding serum BMP-4 levels, whereas BMP-2 levels were significantly higher in the control group (p<0.01). Forty (75.47%) AS patients had serum marker levels measured after anti-TNF-α treatment. No significant change was observed in the serum levels of these 40 patients measured 21.7±6.4 months after the initiation of anti-TNF-α treatment (p>0.05 for all). In AS patients, there was no change in DKK-1/SOST, BMP, and IL-17/23 cascade with anti-TNF-α treatment. This finding may suggest that these pathways act independently of each other, and their local effects are not influenced by systemic inflammation.

353 Amlitelimab reduces serum IL-13 in a phase 2a clinical trial in atopic dermatitis without impacting T-cell expansion in a T-cell recall assay

Abstract Amlitelimab (SAR445229), a fully human non-depleting, non-cytotoxic, monoclonal antibody, binds to OX40Ligand (OX40L) on antigen-presenting cells (APC) to block OX40-OX40L interactions. In a 16-week, double-blind, Phase 2a trial (NCT03754309), amlitelimab induced clinically meaningful disease activity improvement in patients with moderate-to-severe atopic dermatitis (AD). To assess the effects of amlitelimab on interleukin (IL)-13 and T-cell recall responses. In the trial, 89 patients were randomized to amlitelimab low dose (LD; 200 mg loading/100 mg maintenance every 4 weeks [Q4W]), high dose (HD; 500 mg loading/250 mg maintenance Q4W), or placebo. Serum IL-13 levels were assessed by single molecule immunoassay (259 samples). Using human peripheral blood mononuclear cells from five healthy donors, a T-cell recall assay was performed. At baseline in the trial, IL-13 levels significantly correlated with disease severity (Eczema Area and Severity Index; r = 0.4784, P &amp;lt; 0.0001). Week 16 IL-13 levels were significantly reduced with amlitelimab vs. baseline but not placebo (median fold change [95% confidence interval, CI] from baseline to week 16 with P-values based on two-way Analysis of Variance [ANOVA] of log10-transformed fold change for patients with a complete dataset at week 16: LD 0.345 [0.23–0.44], P &amp;lt; 0.0001; HD 0.390 [0.30–0.63], P = 0.0002; placebo 0.835 [0.34–1.12], P = 0.1544). In a T-cell recall assay, amlitelimab significantly reduced IL-13 protein levels at days 3 and 6 without negatively impacting T-cell expansion, based on the percentage of proliferating CD4+ T-cells vs. isotype control. Amlitelimab decreased IL-13 levels in patients with AD and in a T-cell recall assay without negative effects on T-cell expansion, thus reducing inflammation without blocking T-cell proliferation during recall responses.

Is the Level of Pentraxin-3 a Valid Biomarker in Axial Spondyloarthritis?

Abstract Background Pentraxin-3 (PTX-3) is essential in inflammation, remodelling and regulation of inflammation in various rheumatic diseases. This study aimed to determine whether serum PTX-3 levels indicate increased inflammation and disease activity in patients with axial spondyloarthritis (AxSpA). Material and Methods The study comprised 50 AxSpA patients and 20 healthy controls (HC). Serum PTX-3, interleukin (IL)-17 and IL-23 levels were compared between AxSpA patients and the control group. The relationship between PTX-3 levels and acute-phase reactants and disease activity was examined. Disease activity was scored using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score-CRP (ASDAS-CRP). Patients with AxSpA were also separated into two subgroups – non-radiographic AxSpA (nr-AxSpA) and radiographic AxSpA (r-AxSpA) – and compared based on their PTX-3 levels. PTX-3, IL-17 and IL-23 levels were measured using the enzyme-linked immunosorbent assay method. Results PTX-3 levels were higher in patients with AxSpA compared with the HC (2.69±2.03 vs 1.84±1.03 ng/mL, p=0.025). When patients were divided into nr-AxSpA and r-AxSpA subgroups, this difference was found to be only due to patients with r-AxSpA. The r-AxSpA group had significantly higher PTX-3 levels than the nr-AxSpA and HC groups (p=0.020 and p=0.016, respectively). There was no statistically significant difference in PTX-3 levels between the nr-AxSpA and HC groups (p=0.961). There was no correlation between PTX-3 levels and acute-phase reactants, IL-17, IL-23 and disease activity scores (BASDAI and ASDAS-CRP). Conclusion These findings support the hypothesis that PTX-3 levels are higher in patients with r-AxSpA, where chronic inflammation and structural progression are more pronounced and can be used as an inflammation marker. However, they demonstrate that this relationship does not exist in nr-AxSpA and that there is no correlation between disease activity and PTX-3 levels. Thus, PTX-3 levels may be associated with structural changes.

Regulatory B cells protect against chronic hypoxia-induced pulmonary hypertension by modulating the Tfh/Tfr immune balance.

Hypoxia-induced pulmonary hypertension (HPH) is a progressive and lethal disease characterized by the uncontrolled proliferation of pulmonary artery smooth muscle cells (PASMCs) and obstructive vascular remodelling. Previous research demonstrated that Breg cells were involved in the pathogenesis of pulmonary hypertension. This work aimed to evaluate the regulatory function of Breg cells in HPH. HPH mice model were established and induced by exposing to chronic hypoxia for 21 days. Mice with HPH were treated with anti-CD22 or adoptive transferred of Breg cells. The coculture systems of Breg cells with CD4+ T cells and Breg cells with PASMCs in vitro were constructed. Lung pathology was evaluated by HE staining and immunofluorescence staining. The frequencies of Breg cells, Tfh cells and Tfr cells were analysed by flow cytometry. Serum IL-21 and IL-10 levels were determined by ELISA. Protein levels of Blimp-1, Bcl-6 and CTLA-4 were determined by western blot and RT-PCR. Proliferation rate of PASMCs was measured by EdU. Compared to the control group, mean PAP, RV/(LV + S) ratio, WA% and WT% were significantly increased in the model group. Anti-CD22 exacerbated abnormal hemodynamics, pulmonary vascular remodelling and right ventricle hypertrophy in HPH, which ameliorated by adoptive transfer of Breg cells into HPH mice. The proportion of Breg cells on day 7 induced by chronic hypoxia was significantly higher than control group, which significantly decreased on day 14 and day 21. The percentage of Tfh cells was significantly increased, while percentage of Tfr cells was significantly decreased in HPH than those of control group. Anti-CD22 treatment increased the percentage of Tfh cells and decreased the percentage of Tfr cells in HPH mice. However, Breg cells restrained the Tfh cells differentiation and expanded Tfr cells differentiation in vivo and in vitro. Additionally, Breg cells inhibited the proliferation of PASMCs under hypoxic condition in vitro. Collectively, these findings suggested that Breg cells may be a new therapeutic target for modulating the Tfh/Tfr immune balance in HPH.

The Correlation between Interleukin 33 and Psoriasis: A Systematic Review and Meta-Analysis

Psoriasis is a common genetic autoimmune disorder with a global prevalence of 2–3%. The clear pathogenesis of psoriasis is not fully understood, but hyperproliferation and inflammation of the epidermis with marked infiltration of immune cells have been indicated in psoriasis with such cells producing different types of cytokines- interleukin. As such a new member of the IL-1 cytokine family, in some research, IL-33 has been linked with psoriasis showing high serum concentration of IL-33 in human psoriatic plaques compared to normal healthy skin. Despite this, the association between IL-33 and psoriasis is not clear. Herein, in this review, we aim to investigate the correlation between serum IL-33 levels and psoriasis. We conducted meta-analysis using fixed or random-effects models to calculate pooled standard mean differences. We found that the mean IL-33 serum levels were reported between 0.35 pg/mL to 586 pg/mL in the psoriatic group and 0 pg/mL to 87.7 pg/mL in the healthy control group. Out of five, four individual studies included in the analysis reported statistically significant differences in IL-33 levels, the pooled estimate (SMD = 0.340 95% CI: −0.308 to 0.988), however, did not indicate a significant relation between IL-33 and psoriasis. This analysis revealed no significant difference between serum IL-33 levels in the psoriatic population in comparison to healthy controls. This may be because we did not include any animal studies, lab-based studies, any other markers mixed together, or any other cases of diseases mixed together. However, further research is warranted to confirm the reported association as this analysis is limited by the low-quality and observational nature of the included studies.

MicroRNA-30e-3p reduces coronary microembolism-induced cardiomyocyte pyroptosis and inflammation by sequestering HDAC2 from the SMAD7 promoter.

This study investigates the mechanism by which microRNA (miR)-30e-3p reduces coronary microembolism (CME)-induced cardiomyocyte pyroptosis and inflammation. Cardiac function tests, histological staining, and transmission electron microscopy were performed on CME-model rats injected with adeno-associated viral vectors. Cardiomyocytes were transfected 24 h before a cellular model of pyroptosis was established via treatment with 1 μg/mL lipopolysaccharide (LPS) for 4 h and 5 mM ATP for 30 min. Pyroptosis, inflammation, and Wnt/β-catenin signaling in cardiomyocytes were detected. Dual-luciferase reporter assays and/or RNA pull-down assays were performed to verify the binding of miR-30e-3p to HDAC2 mRNA or HDAC2 to the SMAD7 promoter. Chromatin immunoprecipitation was used to assess the level of H3K27 acetylation at the SMAD7 promoter. miR-30e-3p and SMAD7 expression levels were downregulated and HDAC2 expression was upregulated with CME. The overexpression of miR-30e-3p restored cardiac functions in CME-model rats and reduced serum cTnI, IL-18, and IL-1β levels, microinfarcts, inflammatory cell infiltration, apoptosis, collagen content, and GSDMD-N, cleaved caspase-1, and NLRP3 expression in the myocardium, but these effects were reversed by SMAD7 knockdown. The overexpression of miR-30e-3p or knockdown of HDAC2 reduced LDH, IL-18, and IL-1β secretion, propidium iodide intake, and GSDMD-N, NLRP3, cleaved caspase-1, Wnt3a, Wnt5a, and β-catenin expression in the cardiomyocyte model. miR-30e-3p inhibited the expression of HDAC2 by binding HDAC2 mRNA. HDAC2 repressed the expression of SMAD7 by catalyzing H3K27 deacetylation at the SMAD7 promoter. miR-30e-3p, by binding HDAC2 to promote SMAD7 expression, reduces CME-induced cardiomyocyte pyroptosis and inflammation.

Effects of Dupilumab on Itch-Related Events in Atopic Dermatitis: Implications for Assessing Treatment Efficacy in Clinical Practice.

Dupilumab attenuates itch and skin inflammation in patients with atopic dermatitis (AD). However, itch-related events that are improved by dupilumab remain unclear. Therefore, the present study investigated changes in clinical scores, serum biomarkers, and the number of intraepidermal nerve fibers (IENFs) using skin biopsies and blood samples from 12 patients with moderate to severe AD before and after treatment with dupilumab. Clinical manifestations were assessed using eczema area and severity index (EASI) and visual analogue scale (VAS) scores at baseline and after 8 and 16 weeks of treatment. Serum levels of total immunoglobulin E (IgE), thymus and activation-regulated chemokine (TARC), interleukin (IL)-4, IL-13, IL-22, and IL-31 were examined by electrochemiluminescence, chemiluminescent enzyme immunoassays, ProQuantum immunoassays, and enzyme-linked immunosorbent assays (ELISA) at baseline and after 8 and 16 weeks of treatment. In skin biopsies from AD patients at baseline and after 16 weeks of treatment, IENFs were examined immunohistochemically with the anti-protein gene product (PGP) 9.5 antibody. The dupilumab treatment significantly improved EASI and VAS scores and decreased serum levels of TARC, IgE, and IL-22, whereas those of IL-13 and IL-31, and the number of IENFs remained unchanged and those of IL-4 increased. VAS scores were positively correlated with serum TARC, IL-22, and IgE levels and the degree of epidermal thickening. Serum IL-31 levels were positively correlated with the number of IENFs. These results suggest that serum TARC, IL-22, and IgE levels and epidermal thickness are itch-related events associated with dupilumab treatment and that serum IL-31 levels may reflect the degree of IENF density in AD patients. Therefore, dynamic changes may be used to assess the efficacy of dupilumab treatment to treat itching and inflammation in patients with AD.

Interleukin 18 and interleukin 22 as important immune markers in patients with tuberculosis

Tuberculosis (TB) is a lung infection caused by the bacterium Mycobacterium tuberculosis (MTB). TB is a leading cause of death globally, accounting for approximately 1.5 million deaths per year. The aim of this article was to evaluate the immunological role of Interleukin (IL) 18 and Interleukin 22 in patients infected with MTB and multi-drug resistant tuberculosis MDRTB. A total of 182 individuals suspected with MTB admitted to the tuberculosis center in AL-Najaf City, Iraq. A sputum acid-fast stain was performed for each individual and GeneXpert® heminested real time PCR has been performed for MDRTB detection. The two Interleukins was measurement in serum of infected individual using ELISA technique. Out of 182 individuals, there were 20 infected with MTB and 15 infected with MDRTB. Serum IL18 and IL22 levels were significantly elevated (P&lt;0.05) in patients with MTB and MDRTB groups as compared with control subjects. The MDRTB group showed higher serum IL18 and IL22 levels (P&lt;0.05) than the MTB group. This study showed that IL18 and IL22 had a relationship with MTB and might be used to help diagnose TB; Clinical diagnosis of TB may be aided by these tests.

Evaluation of interleukin-33 & sST2 levels in type-2 diabetic mellitus patients with or without metabolic syndrome.

Diabetes mellitus (DM) is characterized by increase in blood glucose levels due to defective insulin secretion or insulin sensitivity. Interleukins (ILs) are known to play an important role in the pathogenesis of DM. The aim of this study was to investigate the serum concentration of IL-33 and its receptor soluble ST2 (sST2) in patients with diabetes and draw a correlation between their serum levels and different standard glycaemic indices of patients affected with type-2 diabetes with or without metabolic syndrome. Thirty type-2 diabetic individuals and 30 healthy controls were recruited for this study. Serum and plasma were separated by centrifugation of blood for quantitative measurement of IL-33, sST2 and other biochemical parameters. It was observed that serum IL-33 levels were significantly less and sST2 levels were significantly high in type-2 diabetic individuals as compared to healthy controls. A significant correlation between the serum IL-33 concentration and fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were also found. Additionally, data also elucidated that serum levels of high-density lipoprotein, low-density lipoprotein or triglyceride in type-2 diabetics did not influence the serum levels of IL-33 and sST2, thereby excluding these factors as the major drivers of changes in serum IL-33 and sST2 concentration. This study demonstrated alteration in serum levels of IL-33 and sST2 in type-2 diabetic individuals. Further mechanistic studies, focusing on the progression of type-2 diabetes could elucidate the involvement of IL-33 in the cellular acquisition of insulin resistance as observed in type-2 diabetics.

Association Abnormal Levels of Serum Interleukin-33, Interleukin-23 with Oxidant-Antioxidants Status in patients with Acute Liver Failure

Acute liver failure (ALF) is not itself a disease, but a condition that develops rapidly in response to some forms of liver injury. There is no evidence to prove an association between serum IL-33 with oxidant- antioxidant status in patients of liver failure. The present study aimed to evaluate the possible association between these parameters and to investigation the prognostic role of interleukin-33 in liver failure disease by using the ROC curve. This study includes (30 patients and 30 controls ((were 17 men and 13 female)). During the period of 2021- 2022, patients and controls aged 30- 55 years. The results showed that there is a significant increase in the serum levels of ( MDA, NO, CP , IL-33 and IL-23) in patients group in comparison with controls group Furthermore, it was found that there is a positive correlation between IL-33 and ( IL-23, MDA, NO and Cp ).The ROC curve demonstrated that the levels of (IL-33, IL-23, MDA, NO and CP) have exhibited an good method for discriminating’ between healthy individuals and patients with acute liver failure .In Conclusion, our findings indicated that there is an association between abnormal serum IL-33 levels and Oxidant-Antioxidants Status. Moreover, the level of IL-33 can consider an early prediction biomarker for gestational diabetes. The use of ROC curve analysis confirmed thatIL-33 is effective for the diagnosis of liver failure.

Combinatory Effect and Modes of Action of Chrysin and Bone Marrow-Derived Mesenchymal Stem Cells on Streptozotocin/Nicotinamide-Induced Diabetic Rats.

The purpose of this study was to see how chrysin and/or bone marrow-derived mesenchymal stem cells (BM-MSCs) affected streptozotocin (STZ)/nicotinamide (NA)-induced diabetic rats as an animal model of type 2 diabetes mellitus (T2DM). Male Wistar rats were given a single intraperitoneal (i.p.) injection of 60 mg STZ/kg bodyweight (bw) 15 min after an i.p. injection of NA (120 mg/kg bw) to induce T2DM. The diabetic rats were given chrysin orally at a dose of 100 mg/kg bw every other day, BM-MSCs intravenously at a dose of 1 × 106 cells/rat/week, and their combination for 30 days after diabetes induction. The rats in the diabetic group displayed impaired oral glucose tolerance and a decrease in liver glycogen content and in serum insulin, C-peptide, and IL-13 levels. They also had significantly upregulated activities in terms of liver glucose-6-phosphatase and glycogen phosphorylase and elevated levels of serum free fatty acids, IL-1β, and TNF-α. In addition, the diabetic rats exhibited a significant elevation in the adipose tissue resistin protein expression level and a significant decrease in the expression of adiponectin, insulin receptor-beta subunit, insulin receptor substrate-1, and insulin receptor substrate-2, which were associated with a decrease in the size of the pancreatic islets and in the number of β-cells and insulin granules in the islets. The treatment of diabetic rats with chrysin and/or BM-MSCs significantly improved the previously deteriorated alterations, with chrysin combined with BM-MSCs being the most effective. Based on these findings, it can be concluded that combining chrysin with BM-MSCs produced greater additive therapeutic value than using them separately in NA/STZ-induced T2DM rats.

Relation between Cytokine Levels and Pulmonary Dysfunction in COVID-19 Patients: A Case-Control Study.

Aim: The study aimed to assess the relationships between serum cytokine levels and pulmonary dysfunctions in individuals with COVID-19. These correlations may help to suggest strategies for prevention and therapies of coronavirus disease. Patients and methods: Fifty healthy participants and one hundred COVID-19 patients participated in this study. COVID-19 participants were subdivided into moderate and severe groups based on the severity of their symptoms. In both patients and healthy controls, white blood cells (WBCs) and lymphocytes counts and serum C-reactive protein (CRP), interleukin (IL)-1, IL-4, IL-6, IL-18, and IL-35 levels were estimated. All the patients were examined by chest computed tomography (CT) and the COVID-19 Reporting and Data System (CO-RADS) score was assessed. Results: All COVID-19 patients had increased WBCs count and CRP, IL-1β, IL-4, IL-6, IL-18, and IL-35 serum levels than healthy controls. Whereas WBCs, CRP, and cytokines like IL-6 showed significantly higher levels in the severe group as compared to moderate patients, IL-4, IL-35, and IL-18 showed comparable levels in both disease groups. Lymphocytes count in all patient groups exhibited a significant decrease as compared to the heathy controls and it was significantly lower in severe COVID-19 than moderate. Furthermore, CO-RADS score was positively connected with WBCs count as well as CRP and cytokine (IL-35, IL-18, IL-6, IL-4 and IL-1β) levels in both groups. CO-RADS score, also demonstrated a positive correlation with lymphocytes count in the moderate COVID-19 patients, whereas it demonstrated a negative correlation in the severe patients. The receiver operator characteristic (ROC) curve analysis indicated that IL-1β, IL-4, IL-18, and IL-35 were fair (acceptable) predictors for COVID-19 in moderate cases. Whereas IL-6 was good predictor of COVID-19 in severe cases (AUC > 0.800), IL-18 and IL-35 were fair. Conclusion: Severe COVID-19 patients, compared to individuals with moderate illness and healthy controls, had lower lymphocyte counts and increased CRP with greater WBCs counts. In contrast to moderate COVID-19 patients, severe COVID-19 patients had higher levels of IL-6, but IL-4, IL-18, and IL-35 between both illness categories were at close levels. IL-6 level was the most potent predictor of COVID-19 progress and severity. CO-RADS 5 was the most frequent category in both moderate and severe cases. Patients with a typical CO-RADS involvement had a higher CRP and cytokine (IL-1β, IL-6, IL-4, IL-18, and IL-35) levels and WBCs count with a lower lymphocyte number than the others. Cytokine and CRP levels as well as WBCs and lymphocyte counts were considered surrogate markers of severe lung affection and pneumonia in COVID 19 patients.

Lacticaseibacillus rhamnosus Probio-M9-Driven Mouse Mammary Tumor-Inhibitory Effect Is Accompanied by Modulation of Host Gut Microbiota, Immunity, and Serum Metabolome.

Gut microbiome may influence tumor growth and cancer treatment efficacy, so it is a potential target for tumor prevention/treatment. This pilot study investigated the preventive and therapeutic effects of a probiotic strain, Lacticaseibacillus rhamnosus Probio-M9 (Probio-M9), against murine mammary cancer. Thirty-six female mice were randomly divided into three groups (n = 12 per group): control (without tumor transplantation), model (tumor transplantation; no probiotic administration), and probiotic (30-day oral gavage of probiotic, started seven days before tumor transplantation). Changes in tumor size were recorded, and blood, tumor tissue, and stool samples were collected at the end of the trial for analyses. Comparing with the model group, the probiotic group had a significantly smaller tumor volume (p < 0.05), a higher fecal microbiota Shannon diversity index, with significant modifications in the gut microbiota structure (p < 0.05), characterized by more Alistipes sp._2, Porphyromonadaceae bacterium_7, and Bacteroidales bacterium 55_9 (p < 0.05). Additionally, Probio-M9 administration elevated the serum IFN-γ, IL-9, IL-13, and IL-27 levels and several metabolites (e.g., pyridoxal, nicotinic acid, 3-hydroxybutyric acid, glutamine; p < 0.05), while reducing IL-5 (p < 0.05). These changes might be associated with the protective effect of Probio-M9 against mammary tumor growth. Thus, probiotic administration could harness host gut microbiome in anti-cancer responses.

Knockout of S1PR3 attenuates acute lung injury in mice by inhibiting the MAPK pathway

To investigate whether knockout of S1PR3 improves lipopolysaccharide (LPS)-induced acute lung injury in mice by inhibiting mitogen activated protein kinases (MAPKs). Male C57BL/6J and S1PR3 knockout (S1PR3-/-) mice were both randomized into two groups (n=8) for intratracheal instillation of normal saline or LPS to induce acute lung injury. The expressions of S1PR3, IL-1β and IL-18 in the lung tissues were detected using RT-qPCR, lung tissue injury was observed with HE staining, and cell apoptosis was detected using flow cytometry. Western blotting was performed to detect the expression levels of caspase-1, GSDMD, p-JNK, p-ERK and p-p38 proteins. In the cell experiment, type II alveolar epithelial cells (MLE-12 cells) were treated with PBS, LPS, CYM5541 (a S1PR3 agonist), or CYM5541 + LPS, and the cell apoptosis and expression levels of MAPK signal pathway molecules were detected. The expression of S1PR3 was up-regulated and serum IL-1β and IL-18 levels were elevated significantly in the nontransgenic mice with acute lung injury (P < 0.001). By comparison, the elevation of IL-1β and IL-18 levels was obviously reduced in S1PR3 knockout mice with acute lung injury, which also showed significant improvement of pulmonary hemorrhage, inflammation and exudation, lowered wet-to-dry ratio of the lungs, and decreased cell apoptosis and expressions of cleaved caspase-1 and GSDMD (P < 0.05). In MLE-12 cells, treatment with the S1PR3 agonist significantly increased the expression of pyroptosis-associated proteins (P < 0.05). S1PR3 knockout strongly inhibited the activation of MAPKs family (JNK and ERK p38; P < 0.05), but their expressions were significantly increased following treatment with the S1PR3 agonist (P < 0.05). Inhibition of S1PR3 can improve LPSinduced acute lung injury in mice by inhibiting the activation of MAPK signaling.

Increased visinin-like protein-1, YKL-40, lipocalin-2, and IL-23 levels in patients with migraine

ABSTRACT Background Migraine is a type of primary headache caused by changes in the trigeminal system and has been reported to be associated with neurovascular inflammation of cerebral and extracerebral vessels. Objective It is known that inflammation is an important process in the pathogenesis of migraine. It has been shown that the molecules of visinin-like protein 1 (Vilip-1), YKL-40, lipocalin-2 and interleukin (IL)-23 play a role in the inflammatory process. Our aim is to investigate the role of this molecule in the metabolic pathway of migraine disease. Methods Fifty migraine patients with and without aura in the interictal period were included in the study. Vilip-1, YKL-40, lipocalin-2, and IL-23 levels were measured by ELISA method. Results Serum vilip-1, YKL-40, lipocalin-2, and IL-23 levels were found to be significantly higher in migraine patients compared to the control group. We found that this molecule increased significantly in migraine subgroups compared to the control group (p < 0.001). A positive significant correlation was found between vilip-1 level and YKL-40 and lipocalin-2 levels in migraine patients. In addition, a positive correlation was observed between visual analogue scale score, number of days with pain and vilip-1 level (p < 0.01). The results of our study showed that activation of inflammatory mediators may play a role in the pathogenesis of migraine disease. In addition, our study is valuable in that inflammatory molecules are high in the interictal period and these biomarkers have never been analyzed in migraine patients. However, we still believe that larger studies are needed to explain the role of vilip-1, YKL-40, lipocalin-2, and IL-23 in the molecular mechanism of migraine disease.

Do increased serum IL-12 and IL-23 levels affect cognitive function in patients with multiple sclerosis? A preliminary study

Aim of the study: To compare the serum levels of IL-12 and IL-23 between healthy volunteers and patients with multiple sclerosis with regard to their cognitive function. Materials and methods: A total of 21 patients with multiple sclerosis and 21 healthy individuals were enrolled into the study. The individuals were age- and sex-matched. Each participant was evaluated using the Montreal Cognitive Assessment (MoCA), the Beck Depression Inventory (BDI), and the Pittsburgh Sleep Quality Index (PSQI). The enzyme-linked immunosorbent assay was performed to assess the serum levels of IL-12 and IL-23. Results: The concentration of IL-12 was 1.61 ± 4.61 pg/mL in the group of patients with multiple sclerosis and 1.78 ± 3.54 pg/mL in the control group, p = 0.5009. The concentration of IL-23 was 19.04 ± 75.50 pg/mL in the study group and 5.50 ± 14.4 pg/mL in the control group, p = 0.5170. A significant difference was found between the control and study groups in the MoCA cognitive test (28 vs. 24 points, respectively, p &lt; 0.0001). There was no significant difference in the Beck Depression Inventory and PSQI between the control and study groups. No significant correlations were found between the IL-12/IL-23 serum levels and psychological evaluations. Conclusions and clinical implications: The results obtained indicate that IL-12 and IL-23 may not play a role in the development of cognitive impairment. The assessment of cognitive impairment in patients with multiple sclerosis may have a screening value in preventing their cognitive deterioration.

Association of Serum Interleukin-17 and Interleukin-23 Levels with Disease Activity, Function, Mobility, Enthesitis Index in Patients with Ankylosing Spondylitis

AbstractAim: More and more studies have demonstrated that the interleukin (IL)-23/IL-17 axis is highly associated with immune dysfunction and activated autoimmune inflammation. The purposes of this study were to determine the serum levels of IL-17 and IL-23 in ankylosing spondylitis (AS) patients compared with healthy controls and evaluate these cytokine levels based on disease-related characteristics. Material and Methods: Eighty-six consecutive AS patients and 70 sex and age-matched healthy controls were included in the study. The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), the Ankylosing Spondylitis Disease Activity Score (ASDAS)-erythrocyte sedimentation rate (ESR), ASDAS-C reactive protein, the Bath Ankylosing Spondylitis Functional Index (BASFI), the Spondyloarthritis Research Consortium of Canada (SPARCC) enthesitis index, the Bath Ankylosing Spondylitis Metrology Index (BASMI), the Ankylosing Spondylitis Quality of Life Questionnaire (ASQoL) and Achilles pain VAS scores were recorded. Serum IL-17 and IL-23 levels were examined by enzyme-linked immunosorbent assay. Results: The serum levels of IL-17, IL-23 and CRP as well as ESR values were significantly increased in AS patients compared with controls (1.94 vs. 0.28 pg/mL p ˂ 0.001; 82.9 vs. 44.3 pg/mL p ˂ 0.001; 0.48 vs. 0.30 mg/dL, p=0.001; 12±13.9 vs. 8±6.8 mm/h, p=0.003, respectively). In AS patients, serum IL-17 levels were significantly correlated with the ASDAS-ESR and ASDAS-CRP (r=0.244, p=0.024; r=0.258, p=0.017), but not with ESR, CRP, BASDAI, function, mobility, quality of life, enthesitis index or Achilles pain scores (all p&gt;0.05). Serum IL-23 levels demonstrated a significant correlation with Achilles pain VAS, but not with other disease-related parameters (all p&gt;0.05). Conclusions: AS patients had increased serum IL-17 and IL-23 levels compared with healthy controls, and serum IL-17 levels were associated with disease activity. Our study results support the hypothesis that the IL17/23 pathway plays an important role in the pathogenesis of AS.