Interleukin-17 Levels Research Articles

Upregulation of Interleukin-33, Human Β-Defensin 2, and Toll-Like Receptor 2 in Response to Staphylococcus aureus Furunculated Patients

A furuncle is an infection of the skin and subcutaneous tissue that involves hair follicles and ultimately results in the formation of an abscess. Furunculosis is most frequently caused by Staphylococcus aureus. interleukin-33, human β defensin 2, and Toll-like receptor 2 (Toll like receptor 2) play a significant role in the innate immunity of the host. The present study aims to determine the level of the interleukin-33, human β defensin 2, and Toll like receptor 2 gene expression in staphylococcal furunculosis. A case-control study includes 50 patients and 50 control were evaluated for the level of interleukin 33, human β defensin and Toll like receptor 2 by enzyme and qPCR, respectively. The results indicated that furunculosis was most prevalent in people between the ages of 25 and 45 (P > 0.05). However, there was no significant difference between males and females (P > 0.05). The serum levels of interleukin-33 were observed to be significantly higher in FP compared to HC. Toll like receptor 2 and human β defensin 2 were elevated in PF, but much more in female patients than in male patients (P < 0.05). In conclusion, the findings of the present study reveal that it is more likely that Toll like receptor 2, human β defensin 2, and interleukin-33 play a significant role in the host's defense against S. aureus infection.

Correlation between Serum Interleukin-33, β2-Microglobulin Levels and DS Stage in Patients with Multiple Myeloma

To investigate the correlation between serum interleukin-33 (IL-33), β2microglobulin (β2-MG) levels and Durie-Salmon (DS) stage in patients with multiple myeloma (MM). 100 MM patients admitted to the First Affiliated Hospital of Fujian Medical University from March 2019 to January 2021 were selected and divided into stage I, stage II and stage III groups according to the DS staging system. A baseline data questionnaire of patients was designed, then the relevant baseline data and laboratory test results of patients were recorded. The levels of serum IL-33 and β2-MG of all patients were detected, and the correlation between serum IL-33, β2-MG levels and DS stage of MM patients was analyzed. Among the 100 patients with MM, there were 32 cases in stage I, 39 cases in stage II and 29 cases in stage III. The levels of serum CRP and β2-MG of patients in stage III were significantly higher than those of patients in stage I and II, and the levels of serum CRP and β2-MG of patients in stage II were significantly higher than those of patients in stage I, the differences were statistically significant (P <0.05). The level of serum IL-33 of patients in stage III was significantly lower than that of patients in stage I and II, and the level of serum IL-33 of patients in stage II was significantly lower than that of patients in stage I, the differences were statistically significant (P <0.05). There was no statistical significant difference in other data between groups (P >0.05). Kendall's tau-b correlation analysis showed that the levels of serum CRP and β2-MG were positively correlated with DS stage in MM patients (r =0.534, 0.776), the level of serum IL-33 was negatively correlated with DS stage in MM patients (r =-0.759). Ordered logistic regression analysis and forest plot showed that the low level of serum IL-33 and the high level of β2-MG were the influencing factors of high DS stage in MM patients (P <0.05 ). DS stage of MM patients is closely related to the levels of serum IL-33 and β2-MG, that is, the lower the serum IL-33 level and the higher the β2-MG level, and the higher the DS stage of MM patients.

UNCONTROLLED BLOOD PRESSURE BEFORE COVID-19 IS ASSOCIATED WITH ELEVATED SERUM IL-17 AND LONG-COVID SEQUELAE IN HEMODIALYSIS PATIENTS

Objective: Hypertension, a nearly ubiquitous complication in hemodialysis (HD) patients, has been identified as a risk factor for COVID -19 and its associated adverse outcomes. In turn, both hypertensive and COVID-19-infected patients with long- COVID sequelae have been reported to have elevated serum interleukin-17 (IL-17) levels. Although HD patients belong to the high-risk group for long COVID sequelae, the association between pre-infection blood pressure (BP) control, serum IL-17 levels, and long COVID sequelae has never been investigated in this cohort. Design and method: A total of 80 HD patients aged 56 (44-63.2) years with a dialysis vintage of 40 (23-74) months who had experienced COVID-19 before enrollment were included in this cross-sectional cohort study. Controlled BP was defined as a 3-month average pre-dialysis BP &lt; 140/90 mmHg and post-dialysis &lt; 130/80 mmHg. IL-17 was measured at least 5 months after acute COVID-19 by ELISA assay. Data were expressed as proportion or median (Me) and interquartile ranges (Q25-Q75) and compared with the Chi-squared test or the Mann-Whitney test as appropriate. Results: Of the 80 patients included, 46 (57.5%) had uncontrolled BP and 34 (42.5%) had controlled BP before infection with COVID -19. Long-term COVID sequelae were observed in 26/46 (56.5%) patients with uncontrolled BP and 11/34 (32.4%) of the BP -controlled group (⇙2 = 4.6, p = 0.03). Serum levels of IL-17 ranged from 0.01 to 15.14 pg/ml and were significantly higher in patients with uncontrolled BP than in the controlled BP group [0.34 (0.08-0.98) vs 0.06 (0.03-0.14) pg/mL, p = 0.001]. In addition, IL-17 was also higher in patients with long-COVID sequelae than in fully recovered patients [0.43 (0.07-1.58) vs 0.08 (0.02-0.16) pg/mL, p = 0.0003], while those with long-COVID sequelae and preinfection uncontrolled BP had the highest value IL-17 (p = 0.04) (Fig. 1). Conclusions: Uncontrolled BP before COVID-19 is associated with increased serum IL-17 levels and long-COVID sequelae in HD patients. Further studies are needed to understand the role of IL-17 in BP control and long-term COVID sequelae in HD patients.

Interleukin 17 and Growth Differentiation Factor 9 Influence in a Sample of Iraqi Infertile Males.

Infertility is defined as the inability of couples to conceive after 1 year of regular unprotected intercourse, which affects 10-15% of couples. The present study aimed to investigate the influence of Interleukin-17 (IL-17) and growth differentiation factor 9 (GDF9) on three groups of infertile males, including control, azoospermia, and oligozoospermia. In total, this study was performed on 93 participants, consisting of 18, 65, and 10 subjects in the Azoospermia, oligozoospermia, and control groups, respectively. The mean plasma levels of IL-17 in the azoospermia and oligozoospermia groups were 21.317±3.605 and 15.101±2.416 ng/l, respectively, which were significantly higher than that in the control group (5.392±1.731 ng/l). Furthermore, the mean plasma levels of GDF9 in the azoospermia and oligozoospermia groups were 3.299±1.051 and 6.2603±2.621 ng/l, respectively, which was significantly higher than that in the control group (12.807±2.170 ng/l). One-way analysis of variance and least significant difference post-hoc test were performed to assess significant differences among means. R-squared measures how well the linear regression model fits the data. It can be interpreted as the proportion of variance of the outcome Y explained by the linear regression model. R-squared is a number between 0 and 1. In non-obstructive forms of severe oligozoospermia and azoospermia, like the case in the current study, intracytoplasmic sperm injection is suggested by using testicular biopsy for spermatozoa extraction, if viable spermatozoa are present.

Analysis of cytokines in bronchoalveolar lavage fluid in patients with checkpoint inhibitor pneumonitis and pulmonary infection: A case-control study.

The discovery of immune checkpoint inhibitors (ICIs) is a breakthrough in the field of cancer therapy. However, ICIs may cause immune-related adverse reactions, including checkpoint inhibitor-related pneumonitis (CIP). The aim of this study was to investigate cytokines in bronchoalveolar lavage fluid (BALF) of patients with CIP compared with patients with pulmonary infection and patients with cancer. We retrospectively analyzed 34 cytokine levels and T cell subsets in BALF supernatant samples from ICI-treated patients with CIP (n = 13), pulmonary infection (n = 10), and progressive cancer (n = 12). Cytokine levels and T cell subsets were compared among the three groups of patients. We observed significantly higher levels of IFN-γ-induced protein 10(IP-10) (p = 0.002), and percentage of CD3 + CD8 + T cells (p = 0.020) in BALF of patients with CIP compared with the other two groups. However, we found significantly lower levels of interleukin-21 (p = 0.008) in BALF of patients with progressive disease compared with the other two groups. Cytokine profile and character of cell subsets in BALF was helpful for the differential diagnosis of CIP. IP-10 may play an important role in pathophysiology for CIP and also be a potential therapeutic target.

Volatile Organic Compounds (VOCs) and Interleukin-23 Levels in Lung Cancer: A Future Biomarker

Introduction: Lung cancer (LC) is the world's second leading cause of death due to malignancy. In Indonesia, LC is one of the top three malignancies. Volatile organic compounds (VOCs) from the respiratory reflect changes in metabolism caused by disease and may be a biomarker of LC. Interleukin-23 (IL-23) has been known as a pro-inflammatory cytokine in the development and progression of cancer. This study aimed to identify levels of IL-23 and VOCs in LC patients. Methods: This study involved 40 LC patients and 42 controls. VOCs were taken by the subject exhaling their third deep breath into the sample bag, which was immediately analyzed using an E-nose-based device. As for the IL-23, the cytokine was taken from the blood serum and then analyzed using the ELISA method. Kolmogorov-Smirnov and Shapiro-Wilk tests were performed to test data normality. Mann-Whitney and Kruskal Wallis tests were conducted for variables. Spearman correlation and heat map were used to find the correlation between the observed gases and IL-23. Results: The concentration of ozone (p = 0.000), ethanol (p = 0.000), formaldehyde (p = 0.000), toluene (p = 0.000), acetone (p = 0.000), ammonia (p = 0.000), ammonium (p = 0.001), nitrogen (p = 0.001) and methane (p = 0.000) in LC group differed with controls. The same outcome was also observed in comparing LC patients and control groups of IL-23 (p = 0.000). Spearman correlation analysis revealed a positive correlation between serum IL-23 with formaldehyde (p = 0.029), toluene (p = 0.014), and ammonia (p = 0.028) and a negative correlation with nitrogen (p = 0.011). Compared to the control group, all types of LC were observed to have higher levels of IL-23. A weak positive correlation was found in formaldehyde (Cv = 0.23), toluene (Cv = 0.23), and ammonia (Cv = 0.13). A weak negative correlation was obtained in acetone (Cv = -0.12), ammonium (Cv = -0.11), and nitrogen dioxide (Cv = 0.23). Conclusion: Weak linear correlations were obtained between the cytokine and formaldehyde, toluene, ammonia, ammonium, and nitrogen dioxide. A higher IL-23 concentration was observed in the LC group than in the control group. The volatile concentration was significantly different between LC and control groups.

Vitamin B6 regulates IL-33 homeostasis to alleviate type 2 inflammation.

Interleukin-33 (IL-33) is a crucial nuclear cytokine that induces the type 2 immune response and maintains immune homeostasis. The fine-tuned regulation of IL-33 in tissue cells is critical to control of the type 2 immune response in airway inflammation, but the mechanism is still unclear. Here, we found that healthy individuals had higher phosphate-pyridoxal (PLP, an active form of vitamin B6) concentrations in the serum than asthma patients. Lower serum PLP concentrations in asthma patients were strongly associated with worse lung function and inflammation. In a mouse model of lung inflammation, we revealed that PLP alleviated the type 2 immune response and that this inhibitory effect relied on the activity of IL-33. A mechanistic study showed that in vivo, pyridoxal (PL) needed to be converted into PLP, which inhibited the type 2 response by regulating IL-33 stability. In mice heterozygous for pyridoxal kinase (PDXK), the conversion of PL to PLP was limited, and IL-33 levels were increased in the lungs, aggravating type 2 inflammation. Furthermore, we found that the mouse double minute 2 homolog (MDM2) protein, an E3 ubiquitin-protein ligase, could ubiquitinate the N-terminus of IL-33 and sustain IL-33 stability in epithelial cells. PLP reduced MDM2-mediated IL-33 polyubiquitination and decreased the level of IL-33 through the proteasome pathway. In addition, inhalation of PLP alleviated asthma-related effects in mouse models. In summary, our data indicate that vitamin B6 regulates MDM2-mediated IL-33 stability to constrain the type 2 response, which might help develop a potential preventive and therapeutic agent for allergy-related diseases.

Imbalance of Peripheral Temperature, Sympathovagal, and Cytokine Profile in Long COVID.

A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies.

Associations between circulating interleukin-17 levels and Behcet's disease and between IL-17 gene polymorphisms and disease susceptibility: a meta-analysis.

To systematically investigate the relationship between circulating interleukin-17 (IL-17) levels and Behçet's disease (BD) and the associations between polymorphisms in IL17 genes and BD susceptibility. We searched the Medline, Embase, and Cochrane databases for relevant articles. We performed a meta-analysis of serum/plasma IL-17 levels in BD patients and controls and evaluated the associations between IL17A rs4711998, rs8193036, and rs2275913 and IL17F rs763780 and rs2397084 polymorphisms and the risk of BD. Twelve studies, involving 901 patients with BD and 1,131 controls, were included. Our meta-analysis revealed that circulating IL-17 levels were significantly higher in the BD group than in the control group (SMD = 1.422, 95% confidence interval [CI] = 0.689-2.155, p<0.001). Subgroup analysis by data type indicated higher IL-17 levels in the BD group in both the original and calculated data populations. Stratification by publication year revealed significantly lower vitamin D levels in the SSc group in both recent and older publication years. No significant differences in IL-17 levels were observed between the active and inactive disease groups. We found no evidence of associations between BD and IL17A rs2275913, L17F rs763780, or rs2397084 polymorphisms. However, a significant association was found between BD and IL17A rs4711998 and rs8193036 polymorphisms in the pooled cohort of affected individuals compared to that in pooled controls (odds ratio [OR] = 1.347, 95% CI = 1.043-1.741, p<0.001; OR = 0.691, 95% CI = 0.542-0.880, p=0.003). This meta-analysis revealed significantly higher circulating IL-17 levels in BD patients and showed evidence of associations between IL17A rs4711998 and rs8193036 polymorphisms and BD.

Naringenin Prevents Renal Injury in Experimental Hyperuricemia Through Suppressing Xanthine Oxidase, Inflammation, Apoptotic Pathway, DNA Damage, and Activating Antioxidant System.

Background/Purpose: This research was performed to determine the effect of naringenin (NAR) in experimental hyperuricemia (HU) induced by potassium oxonate (PO) on uric acid levels and xanthine oxidase (XO), inflammation, apoptotic pathway, DNA damage, and antioxidant system in kidney tissue. Study Design: Wistar Albino rats were categorized into four groups: (1) Control group, (2) PO group, (3) [PO+NAR] (2 weeks) group, and (4) PO (2 weeks)+NAR (2 weeks) group. Methods: The first group was not administered any drug. In group 2, PO was administered intraperitoneally 250 mg/kg/day for 2 weeks. In the third group, 100 mg/kg/day NAR was given intraperitoneally 1 hr after PO injection for 2 weeks. In the fourth group, PO was injected for the first 2 weeks, followed by NAR injection for the second 2 weeks. Serum uric acid levels, XO, nuclear factor-kappa B, tumor necrosis factor-alpha, interleukin-17, cytochrome c, 8-Hydroxydeoxyguanosine (8-OHdG), glutathione peroxidase (GPx), and caspase-3 levels in kidney were determined. Results: HU increased the levels of inflammatory and apoptotic parameters, XO, and 8-OHdG levels in kidney. Administration of NAR caused a decrease in these values and an increase in GPx levels. Conclusions: The results of the study show that NAR treatment reduces serum uric acid levels, and apoptosis, inflammation, and DNA damage; increases antioxidant activity in kidney in experimental HU.

Salivary IL-17 and IL-10 as Potential Diagnostic Biomarkers of Different Stages of Periodontitis in Smoker and Nonsmoker Patients.

The gold standard in the field of periodontal research currently is to find a valid biomarker that can reliably be used for diagnosing periodontal diseases. Given the limitations of the current diagnostic tools that stall to predict susceptible individuals and determine whether active tissue destruction is occurring, there is an increased urge to develop alternative diagnostic techniques that would compensate for the problems inherited in these available methods, such as measuring levels of biomarkers present in oral fluids such as saliva; so the aim of this study was to determine the diagnostic potential of interleukin-17 (IL-17) and IL-10 to differentiate periodontal health from smoker and nonsmoker periodontitis, and to differentiate among different stages (severities) of periodontitis. An observational case-control study was performed on 175 systemically healthy participants grouped into healthy as controls and periodontitis as cases. Periodontitis cases were divided according to the severity into stages I, II, and III, and each of the stages was further subdivided into smokers and nonsmokers patients. Unstimulated saliva samples were collected, clinical parameters were recorded, and salivary levels were assayed using enzyme-linked immunosorbent assay. Elevated levels of IL-17 and IL-10 were associated with stage I and II compared with the healthy controls. However, a significant decrease in stage III was observed compared with the control group for both biomarkers. Salivary IL-17 and IL-10 might be useful for distinguishing periodontal health from periodontitis; however, further research is needed to substantiate their use as potential biomarkers for the diagnosis of periodontitis.

The presence, severity, and onset of preeclampsia is associated with maternal interleukin-23 level: A case-control study.

Scientific evidence support that imbalance between inflammatory and anti-inflammatory cytokines play a critical role in preeclampsia (PE). To investigate the relationship between the maternal serum level of interleukin (IL)-23, a pro-inflammatory cytokine, PE and its severity risk was investigated. The case-control study included a total of 145 women counting 75 PE cases, 35 healthy pregnant and 35 healthy non-pregnant controls from Zahedan, southeast of Iran. The maternal levels of IL-23 in circulation were determined via enzyme-linked immunosorbent assay. The maternal serum levels of IL-23 were increased in PE and its 2 subgroups severe PE and mild PE, so that these increases were significant in PE and severe PE, but not in mild PE compared with the controls (p 0.001 and p 0.001, p = 0.08, respectively). Besides, the maternal IL-23 serum level was statically significant in the early onset PE, but not in the late onset-PE group compared to healthy pregnant controls (p 0.001, p = 0.46 respectively). The results of our study showed a positive association between IL-23 level and PE, especially in severe type and early onset PE, which suggests that IL-23 may be involved in the pathogenesis of this systemic syndrome.

Stress and psoriasis: Exploring the link through the prism of hypothalamo-pituitary-adrenal axis and inflammation

BackgroundPsoriasis is an immune-mediated, chronic inflammatory disease affecting mainly the skin. Chronic stress leads to the blunted hypothalamic-pituitary-adrenal axis (HPA) that might induce pro-inflammatory conditions. Hence, we assessed the blood levels of the HPA hormones and interleukin-17 (IL-17) and the effect of stress and emotional distress to understand the link between stress and psoriasis better. MethodsThis cross-sectional study included 45 patients with psoriasis and 45 age and gender-matched apparently healthy volunteers (n = 45). IL-17, cortisol, and adrenocorticotrophic hormone (ACTH) levels were assessed in both groups. Psoriasis Area Severity Index (PASI) was used to assess disease severity. Presumptive Stressful Life Events scale [PSLE], Perceived Stress scale [PSS] and Daily Hassles and Uplifts Scale [DHUS] scoring were used to assess stress levels and emotional distress. ResultsPatients with psoriasis had higher levels of IL-17 and ACTH and lower levels of cortisol, as compared to controls. Stress scores (PSS, PSLE & DHUS) were significantly elevated in cases, as compared to the controls. IL-17, ACTH and stress scores showed a significant positive correlation with one another and a significant negative correlation with cortisol levels. They also showed a significant positive correlation with PASI, while cortisol levels showed a significant negative correlation. ConclusionPsoriasis patients having high ACTH, IL-17 and stress scores had lower levels of cortisol, indicating a dysregulated HPA axis with the pro-inflammatory state. This might lead to exacerbation of psoriatic flares, which needs investigation in further prospective studies.

Effect and mechanism of Bovis Calculus on ulcerative colitis by inhibiting IL-17/IL-17RA/Act1 signaling pathway

This study aimed to elucidate the effect and underlying mechanism of Bovis Calculus in the treatment of ulcerative colitis(UC) through network pharmacological prediction and animal experimental verification. Databases such as BATMAN-TCM were used to mine the potential targets of Bovis Calculus against UC, and the pathway enrichment analysis was conducted. Seventy healthy C57BL/6J mice were randomly divided into a blank group, a model group, a solvent model(2% polysorbate 80) group, a salazosulfapyridine(SASP, 0.40 g·kg~(-1)) group, and high-, medium-, and low-dose Bovis Calculus Sativus(BCS, 0.20, 0.10, and 0.05 g·kg~(-1)) groups according to the body weight. The UC model was established in mice by drinking 3% dextran sulfate sodium(DSS) solution for 7 days. The mice in the groups with drug intervention received corresponding drugs for 3 days before modeling by gavage, and continued to take drugs for 7 days while modeling(continuous administration for 10 days). During the experiment, the body weight of mice was observed, and the disease activity index(DAI) score was recorded. After 7 days of modeling, the colon length was mea-sured, and the pathological changes in colon tissues were observed by hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), and interleukin-17(IL-17) in colon tissues of mice were detected by enzyme-linked immunosorbent assay(ELISA). The mRNA expression of IL-17, IL-17RA, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, CXCL2, and CXCL10 was evaluated by real-time polymerase chain reaction(RT-PCR). The protein expression of IL-17, IL-17RA, Act1, p-p38 MAPK, and p-ERK1/2 was investigated by Western blot. The results of network pharmacological prediction showed that Bovis Calculus might play a therapeutic role through the IL-17 signaling pathway and the TNF signaling pathway. As revealed by the results of animal experiments, on the 10th day of drug administration, compared with the solvent model group, all the BCS groups showed significantly increased body weight, decreased DAI score, increased colon length, improved pathological damage of colon mucosa, and significantly inhibited expression of TNF-α,IL-6,IL-1β, and IL-17 in colon tissues. The high-dose BCS(0.20 g·kg~(-1)) could significantly reduce the mRNA expression levels of IL-17, Act1, TRAF2, TRAF5, TNF-α, IL-6, IL-1β, CXCL1, and CXCL2 in colon tissues of UC model mice, tend to down-regulate mRNA expression levels of IL-17RA and CXCL10, significantly inhibit the protein expression of IL-17RA,Act1,and p-ERK1/2, and tend to decrease the protein expression of IL-17 and p-p38 MAPK. This study, for the first time from the whole-organ-tissue-molecular level, reveals that BCS may reduce the expression of pro-inflammatory cytokines and chemokines by inhibiting the IL-17/IL-17RA/Act1 signaling pathway, thereby improving the inflammatory injury of colon tissues in DSS-induced UC mice and exerting the effect of clearing heat and removing toxins.

Comparison of Interleukin-33 Serum Levels in Patients with Breast Cancer and Idiopathic Granulomatous Mastitis

Breast cancer (BC) is the main cause of cancer death in women. Idiopathic granulomatous mastitis (IGM), a rare chronic disease that clinically mimics breast carcinoma, and is associated with high mortality and morbidity, but an immediate and accurate diagnosis can substantially decrease these rates. Expressed by numerous human tissues, interleukin-33 (IL-33) has an inductive role in the network of pro-inflammatory cytokines. The aim of this study was to investigate the serum levels of IL-33 in BC and IGM patients in comparison with healthy women. This descriptive-analytical study was carried out on 28 patients with BC and 25 patients with IGM as the patient groups and 25 healthy volunteers with normal screening reports as the control group. Histopathological pattern of BC and IGM were confirmed by specialized pathologists. The serum concentration of IL-33 was measured using enzyme-linked immunosorbent assay (ELISA) kit according to the manufacturer's instructions. The mean age of the patients with BC and IGM and the control group was 49.1, 37.1, and 36.8 years, respectively. There was no significant difference in IL-33 expression among the participants with regard to age, marital status, body mass index (BMI), and menopausal status. IL-33 assay indicated a significant difference between the BC (P=0.011) and IGM (P=0.031) groups compared to the controls, although no substantial differences were observed between the IGM and BC groups. IL-33 can be considered a significant factor distinguishing IGM and BC patients from controls, although it cannot be applied to diagnose and differentiate BC from IGM patients.<br />.

IL-33 promotes inflammatory responses and exacerbates lung pathology in a mouse model of SARS-CoV-2 infection

Abstract The ongoing COVID-19 pandemic caused by SARS-CoV-2 has resulted in more than 6.6 million deaths worldwide as of the end of 2022. Clinical data revealed that dysregulated host immune responses may contribute to disease severity and poor recovery outcomes; however, the mechanisms that underlie immune dysregulation and disease severity are relatively unknown. Interleukin-33 (IL-33), a damage-associated molecular pattern (DAMP) molecule, is mainly expressed in nucleus of epithelial and endothelial cells. Elevated serum IL-33 levels have been recently reported in COVID-19 patients and might be associated with adverse outcomes. In this study, we infected B6 mice with a mouse-adapted SARS-CoV-2 MA10 and found that IL-33 was significantly increased in the lungs at day 2 post-infection, accompanied by highly upregulated inflammatory chemokines CXCL1, CXCL2 and CCL2. Next, we used IL-33 −/−mice and demonstrated that IL-33 deficiency resulted in less bodyweight loss at days 2 and 3 and decreased viral burden at day 4. Flow cytometry analyses showed that IL-33 −/−mice had reduced numbers of innate immune cells at day 2, including neutrophils, macrophages and NK cells. At day 4, IL-33 −/−mice displayed reduced activated T cells in the lungs as compared to WT mice. Lung tissue RNAseq transcriptomics revealed that IL-33 signals contributed to several inflammatory pathways, including type II interferon signaling, pathogen phagocytosis, macrophage activation, cytokine/chemokine and inflammatory responses and oxidative damage. Overall, these data uncover a detrimental role of the DAMP IL-33 in the lungs following SARS-CoV-2 infection and provide new insights to support the development of effective therapeutic strategies for COVID-19. Supported by grants from NIH (R21 AI153586)

Circulating Interleukin-23 Levels in Rheumatoid Arthritis and its Relationship to Disease Activity: a Systematic Review with Meta-Analysis

Background: Rheumatoid arthritis (RA) is a chronic and systemic autoimmune disease that is characterized by severe synovial inflammation, cartilage erosion, bone loss, and generalized vasculopathy. Although the immunologic mechanism of RA is still unclear, it is now thought to be a primarily Th17-driven disease. Along with other factors, IL-23 stimulates the expansion of Th17 cells from naive CD4+ T cells. Objective: The objective of this study is to assess the circulating levels of interleukin (IL)-23 in rheumatoid arthritis (RA) and determine the correlation between plasma/serum IL-23 levels and disease activity. So, we performed a systematic review with meta-analysis comparing plasma/serum IL-23 levels between patients with RA and controls and examined correlation coefficients between circulating IL-23 levels and disease activity Subjects and Methods: Using the following keywords: lenterleukin-23, IL-23, and rheumatoid arthritis, a comprehensive literature search was carried out in the following databases: PubMed, Scopus, Google Scholar, and Web of Science. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses standards were followed, and the review was registered in the PROSPERO International prospective register of systematic reviews with registration number CRD42022345901. Results were reported as standardized mean differences (SMDs) with a 95% confidence interval. All statistical analysis was performed using StatsDirect statistical software version 3.0.0 (StatsDirect Ltd., Cheshire, UK). A sensitivity analysis was conducted using the leave-one-out approach to test the robustness of the results. Results: The total sample size for the RA group included in our review was 408 cases, while the control group sample size was 244 cases. The serum IL-23 level in the RA group was significantly higher than the control group (pooled SMD = 3.5, 95% CI; 2.1: 4.8, P &lt; 0.0001) as compared to the control group. There were 8 studies with a total sample size of 402 that reported the correlation between IL-23 and DAS28-based RA activity. According to our findings, a significantly positive correlation between IL-23 and DAS28-based RA activity was found, with a weighted mean correlation of 0.57 (95% CI; 0.4: 0.75, P &lt; 0.0001). Conclusion: Our meta-analysis has shown that IL-23 circulatory levels are higher in RA patients and that there is a significant positive correlation between IL-23 and disease activity. Our findings emphasize the role that IL-23 may have in RA. More studies may be required to fully comprehend the involvement of IL-23 in RA.

Dissecting the causal association between inflammation and post-traumatic stress disorder: A bidirectional Mendelian randomization study

BackgroundAccumulating evidence showed a bidirectional association between post-traumatic stress disorder and inflammation. However, whether the association is causal remains unclear. We aimed to evaluate the causal relationships between inflammatory cytokines and post-traumatic stress disorder using two-sample bi-directional Mendelian randomization analysis. MethodsSingle nucleotide polymorphism from genome-wide association studies of inflammatory cytokines, C-reactive protein, and post-traumatic stress disorder (23,212 patients and 151,447 controls) was selected as instrumental variables. The causal associations were estimated by inverse variance weighting with sensitivity analyses using weighted median, MR-Egger, and MR-PRESSO methods. ResultsWe observed suggestive associations of genetically predicted interleukin-17 (IL-17) and RANTES with post-traumatic stress disorder. One standard deviation (SD) increase in genetically predicted level of IL-17 lowered the risk of post-traumatic stress disorder with an odds ratio (OR) of 0.902 (95 % CI = 0.828, 0.984, P = 0.02). One SD higher genetically predicted RANTES (CCL5) concentration increased post-traumatic stress disorder risk (OR = 1.067, 95 % CI = 1.005, 1.133, P = 0.032). However, we found no evidence of causal associations of post-traumatic stress disorder with the selected inflammatory cytokines and biomarkers. We observed no evidence supporting the presence of pleiotropy. The results of sensitivity analyses demonstrated the same directions and similar effect sizes as the primary findings. LimitationsPotential pleiotropy, possible weak instruments, and low statistical power limited our findings. ConclusionInflammation was suggestively causally associated with the risk of post-traumatic stress disorder, and inflammatory cytokines had no downstream effect on post-traumatic stress disorder. Further studies are needed to explain the mechanisms of systemic inflammation and neuroinflammation in post-traumatic stress disorder.

Indoleacrylic acid produced by Parabacteroides distasonis alleviates type 2 diabetes via activation of AhR to repair intestinal barrier

BackgroundAnti-inflammatory therapy is an effective strategy in the treatment of type 2 diabetes (T2D). Studies found that inflammatory responses in vivo were strongly associated with defects in the mucosal barrier function of the gut epithelium. While some microbial strains could help repair the intestinal mucosa and maintain the integrity of the intestinal barrier, the specific mechanisms remain to be fully elucidated. The present study investigated the effects of Parabacteroides distasonis (P. distasonis) on the intestinal barrier and the inflammation level in T2D rats and explored the specific mechanisms.ResultsBy analyzing the intestinal barrier function, the inflammatory conditions, and the gut microbiome, we found that P. distasonis could attenuate insulin resistance by repairing the intestinal barrier and reducing inflammation caused by the disturbed gut microbiota. We quantitatively profiled the level of tryptophan and indole derivatives (IDs) in rats and fermentation broth of the strain, demonstrating that indoleacrylic acid (IA) was the most significant factor correlated with the microbial alterations among all types of endogenous metabolites. Finally, we used molecular and cell biological techniques to determine that the metabolic benefits of P. distasonis were mainly attributed to its ability to promote IA generation, active the aryl hydrocarbon receptor (AhR) signaling pathway, and increase the expression level of interleukin-22 (IL-22), thus enhancing the expression of intestinal barrier-related proteins.ConclusionsOur study revealed the effects of P. distasonis in the treatment of T2D via intestinal barrier repairment and inflammation reduction and highlighted a host-microbial co-metabolite indoleacrylic acid that could active AhR to perform its physiological effects. Our study provided new therapeutic strategies for metabolic diseases by targeting the gut microbiota and tryptophan metabolism.

Protective Effects of Selenium Nanoparticles against Bisphenol A-Induced Toxicity in Porcine Intestinal Epithelial Cells.

Bisphenol A (BPA) is widely used to harden plastics and polycarbonates and causes serious toxic effects in multiple organs, including the intestines. Selenium, as an essential nutrient element for humans and animals, exhibits a predominant effect in various physiological processes. Selenium nanoparticles have attracted more and more attention due to their outstanding biological activity and biosafety. We prepared chitosan-coated selenium nanoparticles (SeNPs) and further compared the protective effects, and investigated the underlying mechanism of SeNPs and inorganic selenium (Na2SeO3) on BPA-induced toxicity in porcine intestinal epithelial cells (IPEC-J2). The particle size, zeta potential, and microstructure of SeNPs were detected by using a nano-selenium particle size meter and a transmission electron microscope. IPEC-J2 cells were exposed to BPA alone or simultaneously exposed to BPA and SeNPs or Na2SeO3. The CCK8 assay was performed to screen the optimal concentration of BPA exposure and the optimal concentration of SeNPs and Na2SeO3 treatment. The apoptosis rate was detected by flow cytometry. Real-time PCR and Western blot methods were used to analyze the mRNA and protein expression of factors related to tight junctions, apoptosis, inflammatory responses and endoplasmic reticulum stress. Increased death and morphological damage were observed after BPA exposure, and these increases were attenuated by SeNPs and Na2SeO3 treatment. BPA exposure disturbed the tight junction function involved with decreased expression of tight junction protein Zonula occludens 1 (ZO-1), occludin, and claudin-1 proteins. Proinflammatory response mediated by the transcription factor nuclear factor-k-gene binding (NF-κB), such as elevated levels of interleukin-1β(IL-1β), interleukin-6 (IL-6), interferon-γ (IFN-γ), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α) expression was induced at 6 and 24 h after BPA exposure. BPA exposure also disturbed the oxidant/antioxidant status and led to oxidative stress. IPEC-J2 cell apoptosis was induced by BPA exposure, as indicated by increased BCL-2-associated X protein (Bax), caspase 3, caspase 8, and caspase 9 expression and decreased B-cell lymphoma-2 (Bcl-2) and Bcl-xl expression. BPA exposure activated the endoplasmic reticulum stress (ERS) mediated by the receptor protein kinase receptor-like endoplasmic reticulum kinase (PERK), Inositol requiring enzyme 1 (IRE1α), and activating transcription factor 6 (ATF6). We found that treatment with SeNPs and Na2SeO3 can alleviate the intestinal damage caused by BPA. SeNPs were superior to Na2SeO3 and counteracted BPA-induced tight junction function injury, proinflammatory response, oxidative stress, apoptosis, and ERS stress. Our findings suggest that SeNPs protect intestinal epithelial cells from BPA-induced damage, partly through inhibiting ER stress activation and subsequently attenuating proinflammatory responses and oxidative stress and suppressing apoptosis, thus enhancing the intestinal epithelial barrier function. Our data indicate that selenium nanoparticles may represent an effective and reliable tool for preventing BPA toxicity in animals and humans.