Increased Serum Interleukin-6 Research Articles

Maternal consumption of fish oil protected breast-fed piglets against Escherichia coli lipopolysaccharide-induced damage through reshaping of intestinal fatty acids profile.

It has been well documented that n-3 polyunsaturated fatty acids (n-3 PUFA) can alleviate inflammation caused by Escherichia coli (E. coli) lipopolysaccharides (LPS), the etiologic agents that causing yellow or white dysentery in young pigs. However, it remains unclear whether the increase in n-3 PUFA availability could enhance the ability of nursery pigs to resist invasion by E. coli. LPS. Twenty-four 21-day-old female piglets, each two of them from the same sow fed the beef tallow (BT) or fish oil (FO) diets, were allocated into four treatment groups: BT-CON, piglets from the BT-fed sows and intraperitoneally injected with saline (9 g/L); BT-LPS, piglets from the BT-fed sows and injected with LPS (100 μg/kg body weight); FO-CON, piglets from the FO-fed sows and injected with saline; FO-LPS, piglets from the FO-fed sows and injected with LPS. Following 2 h of LPS challenge, the magnitudes of increase in body temperature approached to a marked (p < 0.01) difference between the BT-CON and BT-LPS piglets, whereas the dramatic (p < 0.01) difference between the FO-CON and FO-LPS piglets was only observed at 4 h post LPS challenge. The body temperature averaged across the time points evaluated was about 0.2°C lower (p < 0.05) in the FO group than in the BT group. The FO group had lower (p < 0.05) mean corpuscular hemoglobin concentration, lower increase in serum interleukin (IL)-1β (p < 0.10) and IL-8 (p < 0.05) levels, higher (p < 0.01) serum albumin concentration, and higher (p = 0.10) ratios of jejunum villus height to crypt depth than the BT group. The FO group had much higher (p < 0.0001) ileal content of C20:5n3, C24:0, and C22:6n3, which were 2-4 times the content of the BT group. LPS challenge resulted in decreased (p < 0.05) intestinal C20:1 and C20:5n3 content, and the decrease (p < 0.05) in intestinal C20:3n6 and C24:1 content was observed in the BT-LPS piglets rather than in the FO-LPS piglets. Taken together, this study indicated that maternal consumption of fish oil protected breast-fed piglets against E. coli LPS-induced damage through reshaping of intestinal fatty acids profile, which sheds new light on the development of nutritional strategies to enhance the ability of young pigs to resist E. coli invasion.

Persistence of SARS-CoV-2 colonization and high expression of inflammatory factors in cardiac tissue 6 months after COVID-19 recovery: a prospective cohort study.

The presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in myocardial autopsy tissues has been observed in certain individuals with coronavirus disease 2019 (COVID-19). However, the duration of cardiac involvement remains uncertain among recovered COVID-19 patients. Our study aims to evaluate the long-term persistence of SARS-CoV-2 within cardiac tissue. We prospectively and consecutively evaluated the patients undergoing mitral valve replacement (MVR) and left atrial (LA) volume reduction surgery from May 25 to June 10, 2023 at our center, who had been approximately 6 months of recovery after Omicron wave. Patients tested positive for SARS-CoV-2 upon admission were excluded. The surgical LA tissue was collected in RNA preservation solution and stored at -80 ℃ immediately. Then SARS-CoV-2, interleukin-6 (IL-6) and interleukin-1β (IL-1β) RNA expression in LA tissues were assessed through thrice-repeated reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analyses. Categorical variables were assessed using the Chi-square or Fisher's exact tests, and continuous variables was analyzed using the Mann-Whitney U test. Nine of 41 patients were enrolled, all of whom tested negative for SARS-CoV-2 upon admission (two antigen and PCR tests). In four of nine patients, SARS-CoV-2 RNA was detected in their LA tissue, indicating viral colonization. Among the four positive cases, the IL-6 and IL-1β relative expression levels in the LA tissue of one patient were increased approximately 55- and 110-fold, respectively, compared to those of SARS-CoV-2 (-) patients. Increased expression of IL-6 and IL-1β were observed in the myocardium of this patient. Another patient demonstrated a remarkable 7-fold increase in both IL-6 and IL-1β expression, surpassing that of SARS-CoV-2 (-) patients. Additionally, no other cardiac inflammation-related diseases or conditions were presented in these two patients. The IL-6 and IL-1β expression levels of the remaining two patients were not significantly different from those of SARS-CoV-2 (-) patients. The relative expression levels of IL-6 and IL-1β in cardiac tissues of all SARS-CoV-2 (-) patients were relatively low. Interestingly, despite abnormally elevated levels of IL-6 and IL-1β within their cardiac tissue, two patients did not show a significant increase in serum IL-6 and IL-1β levels when compared to other patients. Our research suggests that certain COVID-19-recovered patients have persistent colonization of SARS-CoV-2 in their cardiac tissue, accompanied by a local increase in inflammatory factors.

Edible bird's nest alleviates pneumonia caused by tobacco smoke inhalation through the TNFR1/NF-κB/NLRP3 pathway.

Exposure to cigarette smoke directly damages the lungs and causes lung inflammation. The anti-inflammatory properties of edible bird's nest (EBN) have been reported. We aimed to determine the effect of EBN on pneumonia in a mouse model exposed to cigarette smoke. Fifty BALB/c mice were randomly divided into control, model, positive drug, low-dose EBN, and high-dose EBN groups (n = 10 each). Except for the control group, the mice in each group were exposed to four cigarettes once a day for 8 days. In addition, we validated the effects of EBN on A549 cells and investigated the mechanism by which EBN alleviates lung inflammation. Edible bird's nest (EBN) could alleviate the structural damage of lung tissue and the smoke-induced inflammatory response in mice. The best effect was observed at the high dose of EBN (0.019 g). The mice treated with EBN had a stronger ability than those in the model group to resist cigarette smoke stimulation, as indicated by a decrease in serum and lung inflammatory markers (interleukin 6 [IL-6], tumor necrosis factor-α [TNF-α], and interleukin 8 [IL-8]), an increase in serum interleukin 10 (IL-10) levels, and a decrease in the expression of inflammasome NOD-like receptor pyrin 3 (NLRP3). In addition, our cell experiments showed that EBN attenuated cigarette smoke-induced pulmonary inflammation mainly by inhibiting the tumor necrosis factor receptor 1 (TNFR1)/nuclear factor-kappa B (NF-κB)/NLRP3 pathway. These findings provide theoretical evidence for the positive nutritional qualities of EBN for the lung by demonstrating that it inhibits the TNFR1/NF-κB/NLRP3 signaling pathway, which prevents the development of cigarette smoke-induced pulmonary inflammation.

Effects of potassium sorbate on systemic inflammation and gut microbiota in normal mice: A comparison of continuous intake and washout period

Potassium sorbate (PS) is a widely used food preservative in the field of food industry. However, the effects of continuous intake and washout period of PS on host health are still unclear. In this study, to investigate long-term effect and after-effect of different concentrations and time points of PS, healthy mice were orally exposed to 150 mg/kg, 500 mg/kg and 1000 mg/kg of PS for 10 weeks, and washout treatment for another 5 weeks, respectively. The results indicated that PS intake for 10 weeks had no obvious effects on organs and adipose tissue, nor did it noteworthily interfere with glucolipid metabolism in the serum. However, it caused inflammatory cell infiltration in the liver, increased serum interleukin (IL)-1β level, changed abundances of gut microbiota but failed to promote the production of short chain fatty acids in the gut. After washout period for 5 weeks, liver inflammation and IL-1β level were decreased, and gut environment developed towards a healthier condition. Specifically, PS washout significantly increased abundance of Lachnospiraceae_NK4A136_group and the production of isobutyric acid. This study confirmed washout period eliminated negative effects from continuous intake of PS, which provided positive evidence for its safety.

Synbiotics improve growth performance and nutrient digestibility, inhibit PEDV infection, and prevent intestinal barrier dysfunction by mediating innate antivirus immune response in weaned piglets.

This experiment was conducted to explore the effects of dietary synbiotics (SYB) supplementation on growth performance, immune function, and intestinal barrier function in piglets challenged with porcine epidemic diarrhea virus (PEDV). Forty crossbred (Duroc × Landrace × Yorkshire) weaned piglets (26 ± 1d old) with a mean body weight (BW) of 6.62 ± 0.36kg were randomly allotted to five groups: control (CON) I and CONII group, both fed basal diet; 0.1% SYB group, 0.2% SYB group, and 0.2% yeast culture (YC) group, fed basal diet supplemented with 0.1%, 0.2% SYB, and 0.2% YC, respectively. On day 22, all piglets were orally administrated with 40mL PEDV (5.6 × 103 TCID50/mL) except piglets in CONI group, which were administrated with the same volume of sterile saline. The trial lasted for 26d. Before PEDV challenge, dietary 0.1% SYB supplementation increased final BW, average daily gain (ADG), and decreased the ratio of feed to gain during 0 to 21d (P < 0.05), as well as improved the apparent nutrient digestibility of dry matter (DM), organic matter (OM), crude protein, ether extract (EE), and gross energy (GE). At the same time, 0.2% YC also improved the apparent nutrient digestibility of DM, OM, EE, and GE (P < 0.05). PEDV challenge increased diarrhea rate and diarrhea indexes while decreased ADG (P < 0.05) from days 22 to 26, and induced systemic and intestinal mucosa innate immune and proinflammatory responses, destroyed intestinal barrier integrity. The decrease in average daily feed intake and ADG induced by PEDV challenge was suppressed by dietary SYB and YC supplementation, and 0.1% SYB had the best-alleviating effect. Dietary 0.1% SYB supplementation also increased serum interleukin (IL)-10, immunoglobulin M, complement component 4, and jejunal mucosal IL-4 levels, while decreased serum diamine oxidase activity compared with CONII group (P < 0.05). Furthermore, 0.1% SYB improved mRNA expressions of claudin-1, zonula occludens protein-1, mucin 2, interferon-γ, interferon regulatory factor-3, signal transducers and activators of transcription (P < 0.05), and protein expression of occludin, and downregulated mRNA expressions of toll-like receptor 3 and tumor necrosis factor-α (P < 0.05) in jejunal mucosa. Supplementing 0.2% SYB or 0.2% YC also had a positive effect on piglets, but the effect was not as good as 0.1% SYB. These results indicated that dietary 0.1% SYB supplementation improved growth performance under normal conditions, and alleviated the inflammatory response and the damage of intestinal barrier via improving innate immune function and decreasing PEDV genomic copies, showed optimal protective effects against PEDV infection.

Curcumin: Compound in Turmeric that Has the Potential to Increase Serum Interleukin-10 (IL-10) Levels After High-Intensity Exercise

This study aims to analyze the effect of curcumin on serum IL-10 levels after high-intensity exercise. This experimental research uses pre and post-control group design. Research subjects were selected using purposive sampling technique. Next, the subjects were divided into 2 groups, namely group (K1) given placebo and group (K2) given curcumin. A total of 20 healthy men participated in this study who were selected based on inclusion and exclusion criteria. On the first day, all subjects collected data on the characteristics of the research subjects, then warmed up, then the subjects did exercises in the form of squad exercises and leg presses with an intensity of 80-90% of their maximum ability. Exercises are done in 4 sets, 10 repetitions for each form of exercise and rest between sets for approximately 60 seconds. On the second day, after 24 hours, all subjects had pre-test blood samples taken to measure serum IL-10 levels and were given intervention according to group. On the third day, after 24 hours, all subjects had post-test blood samples taken to measure serum IL-10 levels. Blood samples were analyzed in the laboratory using the ELISA method with the Human IL-10 ELISA kit catalog number MDBEH6154. The results of this study reported that the group given curcumin at a dose of 400 mg had significantly increased serum IL-10 levels (p&lt;0.05). Increasing serum IL-10 levels, which is an anti-inflammatory cytokine, has the potential to control uncontrolled inflammation after exercise. So in this case, the anti-inflammatory properties of curcumin also have the potential to reduce post-exercise muscle pain. Reducing the intensity of pain after high intensity exercise is necessary to support body function. Keywords: Curcumin, Inflammation, Cytokines, Pain Intensity, Exercise

Multiple Myeloma Induced IL-6 Reprograms Lipid Metabolism through a CD36 Dependent Mechanism

Multiple Myeloma (MM) requires a high metabolic turnover to allow for expansion and paraprotein production. MM metabolism is complex relying on various metabolic pathways to fuel its survival including fatty acid (FA) oxidation (1, 2). The liver is a master regulator of fatty acid metabolism and distribution. It also stores FA as lipid droplets during steady state or produces ketone bodies during a starvation state (3). This study aimed to determine whether MM alters FA uptake within the liver and by what mechanism this occurs. To investigate the role of FA metabolism we used a mouse model of MM (5TGM1 (GFP) cells into KaLwRij mice). Analysis of serum from 5TGM1 (GFP) engrafted KaLwRij mice showed increased FFA when compared to control animals. RT-qPCR of RNA isolated from liver samples showed a decrease in genes involved in FA uptake and metabolism. These genes included the long chain fatty acid transporter CD36, which belongs to the class B scavenger receptors and is essential for uptake of LCFA in hepatocytes. In vitro modelling showed that primary hepatocytes cultured in conditioned media from 5TGM1 cells had significantly reduced expression of CD36. Furthermore, serum isolated from MM patients (n=6) downregulated CD36 expression in the human hepatocarcinoma cell line, HepG2. These data support the hypothesis that MM induces a factor that alters lipid metabolism in the liver. To detemine the factor that MM secretes, and which regulates FA uptake in the liver, a cytokine array of the serum from 5TGM1 (GFP) engrafted KaLwRij mice was compared to control serum. Pathway analysis revealed interleukin-6 (IL-6) as possible key factor involved in regulating liver FA uptake. In vitro gene expressions analysis of mouse primary hepatocytes revealed that addition of IL-6 to the medium inhibited expression of CD36 and also showed that primary hepatocytes had decreased reliance on FA oxidation when treated with IL-6. Furthermore. 5TGM1 (GFP) engrafted KaLwRij mice showed increased serum IL-6 levels compared to controls. Finally, using the IL-6 neutralising antibody, we observed that this blocked CD36 downregulation in HepG2 cultured with MM patient serum. Here we demonstrate that MM changes FA metabolism in the liver through upregulation of IL-6. Gene expression of FA genes identifies CD36 is down regulated in hepatocytes in response to IL-6. These data suggest that MM is able to redirect FFA away from the liver by down regulating CD36, which mediates FFA uptake in the liver. References Panaroni C, Fulzele K, Mori T, Siu KT, Onyewadume C, Maebius A, et al. Multiple myeloma cells induce lipolysis in adipocytes and uptake fatty acids through fatty acid transporter proteins. Blood. 2022;139(6):876-88.Tirado-Vélez JM, Joumady I, Sáez-Benito A, Cózar-Castellano I, Perdomo G. Inhibition of fatty acid metabolism reduces human myeloma cells proliferation. PLoS One. 2012;7(9):e46484.Hodson L, Gunn PJ. The regulation of hepatic fatty acid synthesis and partitioning: the effect of nutritional state. Nat Rev Endocrinol. 2019;15(12):689-700.

Post-Operative Increase in Serum Interleukin-6 Is Associated With Longer Hospital Stay in Children Operated on for Acute Appendicitis: A Pilot Study.

Background: Pediatric acute appendicitis (PAA) involves a substantial consumption of health and economic resources. The identification of serum biomarkers that may help predict the post-surgical evolution of these patients is a field of great interest. Patients and Methods: This was a prospective, observational substudy within the Biomarkers for the Diagnosis of Appendicitis in Pediatrics (BIDIAP) cohort aimed at evaluating the association between post-surgical increase in serum IL-6 and different outcomes related to the clinical evolution of children operated on for PAA. Sixty-nine children with a confirmed diagnosis of acute appendicitis and both pre-operative and post-operative serum IL-6 were included in the study. Three multivariable-adjusted linear regression models were fitted to analyze the association between an increase of >10% in post-operative serum IL-6 level with the length of stay, the number of post-operative emetic episodes, and the onset of oral feeding. Two multivariable-adjusted logistic regression models were fitted to assess the association of the same exposure with the indication of antibiotherapy at discharge and with positivity in peritoneal fluid culture. Results: Thirteen children showed an increase of >10% in the post-operative serum IL-6 value (group 1) whereas 56 showed only a minor increase, or no change (group 2). After accounting for potential confounders, children in group 1 had a mean of three-day longer hospital stay (difference, 3.33; 95% confidence interval [CI], 0.57-6.09) and higher odds of a positive result in peritoneal fluid culture (odds ratio [OR], 37.43; 95% CI, 1.02-1361.28) than children in group 2. Conclusions: An increase of >10% in post-operative serum IL-6 value could predict longer hospital stay and higher odds of positive peritoneal fluid culture. Future prospective studies are needed to replicate these findings and to broaden the range of biomarkers that could predict the post-operative evolution of children operated on for PAA.

A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2.

Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95). ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay. Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment versus SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels. Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.

Increased serum interleukin-6 and lactate dehydrogenase levels among nonsurvival severe COVID-19 patients when compared to survival ones

BackgroundAccurate and rapid laboratory diagnosis of COVID-19 infection and its deterioration is one of the milestones of pandemic control. Therefore, this study aimed to compare the diagnostic and prognostic accuracy of the mainly used laboratory biomarkers (WBCS, neutrophil and lymphocyte percentages, CRP, ferritin, IL-6, D-dimer, procalcitonin, and LDH) in the sera of severe COVID-19 Egyptian patients to assess the most appropriate biomarker used in severe COVID-19 patients. MethodsA total of 180 unvaccinated severe COVID-19 patients were enrolled in our study. Demographic data, hospitalization time, medical history, oxygen saturation, respiratory rate, oxygen supply, laboratory findings, and thorax tomography of the patients were obtained retrospectively from the hospital's electronic information system. ResultsOur results revealed that the levels of neutrophil percentage, CRP, IL-6, PCT, and LDH were significantly increased while lymphocyte percentage was significantly decreased among nonsurvival severe COVID-19 patients when compared with survival ones. By using ROC curve analysis, IL-6, and LDH are the most sensitive and specific markers for the prediction of bad prognosis and mortality among severe COVID-19 patients with 100% and 93% sensitivity and 93.7% specificity; respectively. IL-6 and LDH showed significant correlations with the other parameters, which suggested their association with the severity of COVID-19. ConclusionBy using survival severe COVID-19 patients as a control group, our results showed that blood neutrophil percentage, serum CRP, IL-6, PCT, and LDH were significantly increased in non-survivors as compared to survivors. As biomarkers, our results revealed that IL-6 and LDH are good predictors of mortality among severe COVID-19 patients.

Increased Serum Interleukin 10 Levels Are Associated with Increased Disease Activity and Increased Risk of Anti-SS-A/Ro Antibody Positivity in Patients with Systemic Lupus Erythematosus.

To evaluate the association between serum IL-10 levels and autoantibodies, disease activity and organ involvement in systemic lupus erythematosus (SLE) patients. We studied 200 SLE patients and 50 controls. We analyzed organ involvement, disease activity, serum IL-10 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. Serum IL-10 and IL-6 levels were higher in SLE patients than in controls (all p < 0.00001). Serum IL-10 levels were positively correlated with IL-6 (p < 0.00001), CRP (p < 0.00001), fibrinogen (p = 0.003), and ESR (p < 0.00001), and negatively correlated with hemoglobin (p = 0.0004) and lymphocytes (p = 0.01). Serum IL-6 levels were positively correlated with CRP (p < 0.00001), fibrinogen (p = 0.001), and ESR (p < 0.00001); and negatively correlated with hemoglobin (p = 0.008) and lymphocytes (p = 0.03). Elevated serum IL-10 levels were associated with an increased risk of anti-SS-A/Ro antibody positivity (p = 0.03). Elevated serum IL-6 levels were associated with an increased risk of heart (p = 0.007) and lung (p = 0.04) involvement. In SLE patients, increased serum IL-10 levels were associated with increased disease activity and risk of anti-SS-A/Ro antibody positivity.

Diagnostic accuracy of inflammation and insulin resistance markers in non-alcoholic fatty liver disease in children

Background. Insulin resistance indices, in particular homeostatic model assessment of insulin resistance (HOMA-IR), and circulating cytokines are promising markers for noninvasive assessment of hepatocyte damage and metabolic risk in non-alcoholic fatty liver disease (NAFLD) in children and can be used to select pediatric patients at risk of adverse disease course. The purpose was to determine the diagnostic accuracy of insulin resistance markers and circulating cytokines in non-alcoholic fatty liver disease in children. Materials and methods. One hundred and seventy patients aged 6–17 (average of 12.15 ± 2.51) years were included in the study. Hepatic steatosis was determined by transient elastography. Patients were divided into 4 groups according to the presence of hepatic steatosis, non-alcoholic steatohepatitis (NASH) and obesity: group 1 — 37 obese children with NASH, group 2 — 53 patients with simple steatosis, group 3 — 65 obese children without steatosis, group 4 (controls) — 15 patients with normal weight without NAFLD. Anthropometric parameters, carbohydrate metabolism with the HOMA-IR calculation, cytokine profile were evaluated. Results. An increase in serum interleukin (IL) 6 and tumor necrosis factor (TNF) α levels in NAFLD children compared to the control group (p &lt; 0.05), a decrease in IL-10 level in patients with NAFLD (p &lt; 0.05), and an increase in TNFα/IL-10 ratio (p &lt; 0.05) in NASH children compared to obese patients without steatosis were demonstrated. In NAFLD children, an increase of HOMA-IR was found compared to the controls and obese patients without steatosis (p &lt; 0.05). The threshold value of HOMA-IR for the diagnosis of simple steatosis was 3.6 (sensitivity 78.6 %, specificity 52.0 %, area under the curve (AUC) 0.687), for the diagnosis of NASH — 4.9 (sensitivity 77.5 %, specificity 61.7 %, AUC 0.750). The threshold value of TNFα/IL-10 ratio for the diagnosis of NASH was 0.58 (sensitivity 75.7 %, specificity 65.7 %, AUC 0.716). Conclusions. The threshold values of HOMA-IR and TNFα/IL-10 ratio demonstrate high diagnostic accuracy and can be used for early non-invasive diagnosis of NAFLD in obese children and for differential diagnosis of simple steatosis and NASH.

Increased serum interleukin 22 levels in patients with axial spondyloarthritis

Objectives The role of IL-22 in radiographic axial spondyloarthritis is not fully elucidated. Thus, there is a need for new insights into this cytokine in this disease. We aimed to compare interleukin (IL)-22 level between spondyloarthritis, non-specific-low back pain patients, and pain-free controls, and to evaluate associations between this cytokine and spondyloarthritis characteristics. Methods We conducted a case-control study including 62 patients with radiographic axial spondyloarthritis(G1), 46 with non-specific low back pain(G2), and 42 healthy volunteers(G3). IL-22 was measured using Enzyme-linked immunosorbent assay. We evaluate disease activity and structural damage of spondyloarthritis. Results IL-22 level was higher in G1 than in G2 and G3 (38±40 versus14.42± 8.17 versus 14.3±18.67pg/mL,p<0.01). IL-22 discriminated patients in G1 from G2 with a cutoff of 22.28pg/mL (Sensitivity:62.9%, Specificity:97.8%, area under the curve (AUC): 0.808). IL-22 cutoff of 19.27pg/mL discriminated patients in G1 from G3 (Sensitivity: 67%, Specificity:94.3%, AUC:0.855). No associations were found between IL-22 levels and disease activity and structural damage. Conclusions : Our study showed that IL-22 level was higher in radiographic axial spondyloarthritis patients compared to controls. It was also able to differentiate G1 patients from G2 and G3. This finding suggests that the IL-22 pathway showed to play a pathological role in spondyloarthritis.

Antimicrobial Activity of Tannic Acid In Vitro and Its Protective Effect on Mice against Clostridioides difficile.

Clostridioides difficile infection (CDI), recurrently reported as an urgent threat owing to its increased prevalence and mortality, has attracted significant attention. As the use of antibiotics to treat CDI has many limitations, such as high recurrence rate, the need to actively seek and develop other drugs that can effectively treat CDI with fewer side effects has become a key issue in CDI prevention and treatment. This study aimed to evaluate the inhibitory effect of Galla chinensis (GC) and its main component, tannic acid (TA), against C. difficile in vitro and its therapeutic effect on CDI in vivo. When GC and TA concentrations were 250 and 64 mg/L, respectively, the cumulative antibacterial rate against C. difficile reached 100%. The sub-MIC of TA significantly inhibited C. difficile sporulation, toxin production, and biofilm formation in vitro. Compared with the CDI control group, TA-treated mice lost less weight and presented a significantly improved survival rate. TA significantly reduced the number of spores in feces, decreased serum TcdA level, and increased serum interleukin 10 (IL-10). Based on the inhibitory effect of TA on C. difficile in vitro and its therapeutic effect on the CDI mouse model, we consider TA as a potentially effective drug for treating CDI. IMPORTANCE Clostridioides difficile is one of the major pathogens to cause antibiotic-associated diarrhea. Although antibiotic treatment is still the most commonly used and effective treatment for CDI, the destruction of indigenous intestinal microbiota by antibiotics is the main reason for the high CDI recurrence rate of about 20%, which is increasing every year. Moreover, the growing problem of drug resistance has also become a major hidden danger in antibiotic treatment. GC has been used to treat diarrhea in traditional Chinese medicine. In the present study, we evaluated the inhibitory effect of TA, the main component of GC, on dissemination and pathogenic physiological functions of C. difficile in vitro, as well as its therapeutic efficacy in a CDI model. Overall, TA is considered to be a potentially effective drug for CDI treatment.

Apigenin Ameliorates Hyperuricemia and Renal Injury through Regulation of Uric Acid Metabolism and JAK2/STAT3 Signaling Pathway.

Hyperuricemia (HUA) is a kind of metabolic disease with high incidence that still needs new countermeasures. Apigenin has uric-lowering and kidney-protective activities, but how apigenin attenuates HUA and renal injury remains largely unexploited. To this end, an acute HUA mouse model was established by intraperitoneal injection of potassium oxazinate and oral administration with hypoxanthine for 7 consecutive days. Apigenin intervention decreased serum uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor (TNF-α), interleukin-18 (IL-18), liver xanthine oxidase (XOD), and urine protein levels, and increased serum interleukin-10 (IL-10) and urine UA and CRE levels in HUA mice. Moreover, administration of apigenin to HUA mice prevented renal injury, decreased renal glucose transporter 9 (GLUT9) and urate anion transporter 1 (URAT1) levels, and increased renal organic anion transporter 1 (OAT1). These alterations were associated with an inhibition of IL-6, phospho-janus kinase 2 (P-JAK2), phospho-signal transducer, and activator of transcription 3 (P-STAT3), and suppression of cytokine signaling 3 (SOCS3) expression in the kidneys. Additionally, the molecular docking results showed that apigenin had strong binding capacity with UA transporters and JAK2 proteins. In summary, apigenin could improve UA metabolism and attenuate renal injury through inhibiting UA production, promoting excretion, and suppressing the JAK2/STAT3 signaling pathway in HUA mice. The results suggest that apigenin may be a suitable drug candidate for management of HUA and its associated renal injury.

Follow-up of Interleukin 6 and Other Blood Markers during the Hospitalization of COVID-19 Patients: A Single-Center Study

COVID-19 is a recent respiratory illness with high morbidity and mortality; therefore, the study and characterization of blood markers associated with the improvement or deterioration of COVID-19 patients are crucial. This study compared levels of interleukin 6 (IL-6), procalcitonin (PCT), D-dimer, cortisol, dehydroepiandrosterone sulfate (DHEA-S), c-reactive protein (CRP), 25-OH vitamin D, anti-SARS-CoV-2 IgG antibodies, and viremia in mild–moderate and severe–critical COVID-19 patients. In addition, the time course of blood markers was studied in severe–critical cases. The results show that levels of IL-6, PCT, D-dimer, and CRP, the cortisol/DHEA-S ratio, as well as positive viremia and anti-Spike IgGs were higher in severe–critical patients requiring hospitalization. During follow-up, most severe–critical cases displayed similar time patterns of IL-6 and viral load, whereas anti-SARS-CoV-2 antibody curves showed an inverse pattern. A decrease in IL-6 levels was associated with the improvement of COVID-19 patients, mostly through a reduced oxygen requirement. This preliminary study suggests that an increase in serum IL-6, PCT, D-dimer and CRP levels and the cortisol/DHEA-S ratio could support the selection of patients with poorer prognosis and the need for an intensive or alternative treatment. Additionally, changes in IL-6 during hospitalization were associated with changes in patient’s status mainly with a decrease in oxygen requirements, which indicates that serial measurements of IL-6 could predict the outcome of severe–critical patients with COVID-19 pneumonia.

Acute arsenic exposure exacerbates lipopolysaccharide-induced lung injury possibly by compromising the integrity of the lung epithelial barrier in rats

Inhalation of large amounts of arsenic can damage the respiratory tract and may exacerbate the development of bacterial pneumonia, but the exact mechanism remains unclear. In this study, male Wistar rats were randomly divided into control, arsenic trioxide (16.0 μg/kg ATO), lipopolysaccharide (0.5 mg/kg LPS), and ATO combined with LPS (16.0 μg/kg ATO + 0.5 mg/kg LPS) groups. Blood and lung tissue samples were collected from each group 12 h after exposure. The results showed that exposure to ATO or LPS alone produced different effects on leukocytes and inflammatory factors, while combined exposure significantly increased serum interleukin-6, interleukin-10, lung water content, lung lavage fluid protein, and p38 protein phosphorylation levels. Alveolar interstitial thickening, alveolar membrane edema, alveolar type I and II cell matrix vacuolization, and nuclear pyknosis were observed in rats exposed to either ATO or LPS. More severe ultrastructural changes were found in the combined exposure group, and chromatin splitting was observed in alveolar type I cells. Lanthanum nitrate particles leaked from the alveolar vascular lumen in the ATO-exposed group, whereas in the combined exposure group, Evans Blue levels were increased and lanthanum nitrate particles were present in the lung parenchyma. Claudin-3 protein expression increased and claudin-4 expression decreased after ATO or LPS exposure, while claudin-18 expression was unchanged. The changes in claudin-3 and claudin-4 protein expression were further exacerbated by combined exposure. In conclusion, these results suggest that inhalation of ATO may exacerbate the development of bacterial pneumonia and that common mechanisms may exist to synergistically disrupt epithelial barrier integrity.

The monoacylglycerol lipase inhibitor, JZL184, has comparable effects to therapeutic hypothermia, attenuating global cerebral injury in a rat model of cardiac arrest

Post-resuscitation cerebral ischemia-reperfusion injury (IRI) is a vital contributor to poor neurological prognosis. Exploring novel therapeutics that attenuate cerebral IRI is of great significance. Inflammation plays a role in the development of cerebral IRI after successful cardiopulmonary resuscitation (CPR). Monoacylglycerol lipase (MAGL) is an enzyme that is predominantly responsible for the metabolism of endocannabinoid 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) metabolites, which are associated with inflammation. Therefore, we investigated the efficacy of the MAGL inhibitor, JZL184, on cerebral IRI and further compared the effects to therapeutic hypothermia (TH). Thirty-six rats were randomized into three groups: 1) JZL184; 2) Control; 3) TH (N = 12 for each group). Animals underwent 6 min of ventricular fibrillation (VF) followed with 8 min of CPR. After return of spontaneous circulation (ROSC), rats received an intraperitoneal injection of JZL184 (16 mg/kg) or DMSO (20 mg/ml) or body cooling was initiated. Cerebral microcirculation, brain edema, blood brain barrier (BBB) permeability, serum neuron-specific enolase (NSE), S-100β, interleukin-6 (IL-6) and interleukin-10 (IL-10) were quantified at 6 h post ROSC. Compared to control, treatment with JZL184 or TH was associated with significantly ameliorated cerebral microcirculation, mitigated brain edema, attenuated BBB permeability, decreased serum levels of NSE, S-100β and IL-6, and increased serum IL-10 levels (p < 0.05). There was no significant difference in the above measurements between JZL184 and TH. JZL184 has comparable neuroprotective effects to therapeutic hypothermia on global cerebral IRI in a rat model of cardiac arrest (CA).

Ultra-Sensitive and Semi-Quantitative Vertical Flow Assay for the Rapid Detection of Interleukin-6 in Inflammatory Diseases.

The inflammation biomarker Interleukin 6 (IL-6) exhibits a concentration of less than 7 pg/mL in healthy serum but increases 10–100-fold when inflammation occurs. Increased serum IL-6 has been reported in chronic diseases such as rheumatoid arthritis (RA), as well as in life-threatening acute illnesses such as sepsis and cytokine release syndrome (CRS). This work seeks to meet the demand for rapid detection of serum IL-6 both for rapid monitoring of chronic diseases and for triaging patients with acute illnesses. Following the optimization of several types of gold nanoparticles, membrane pore sizes, and buffer systems, an ultra-sensitive vertical flow assay (VFA) was engineered, allowing the detection of recombinant IL-6 in spiked buffer with a limit of detection (LoD) of 10 pg/mL and a reportable range of 10–10,000 pg/mL with a 15-min assay time. The detection of IL-6 in spiked pooled healthy serum exhibited an LoD of 3.2 pg/mL and a reportable range of 10–10,000 pg/mL. The VFA’s stability was demonstrated over 1-day, two-week, four-week, and six-week storage durations at room temperature. The inter-operator CV and intra-operator CV were determined to be 14.3% and 15.2%, respectively. Three reference zones, high, low, and blank, were introduced into the cartridge to facilitate on-site semi-quantitative measurements across a 6-point semi-quantitative range. Finally, the performance of the IL-6 VFA was validated using 20 RA and 20 healthy control (HC) clinical serum samples, using ELISA as the gold standard platform. The ultra-sensitive, rapid IL-6 VFA could potentially be used to triage patients for intensive care, treatment adjustments, or for monitoring disease activity in inflammatory conditions.

Klotho relieves inflammation and exerts a cardioprotective effect during renal ischemia/reperfusion-induced cardiorenal syndrome

BackgroundRenal ischemia and reperfusion injury (IRI) is the main cause of acute kidney injury (AKI). AKI induces the development of cardiac hypertrophy (CH) during cardiorenal syndrome (CRS), and cardiomyocyte calcium mishandling though systemic inflammation after 8 days of renal IRI. Klotho has recently been described as an anti-inflammatory component. Given this, Klotho treatment could prevent or attenuate the inflammation, thereby also preventing electrical cardiac outcomes incurred by CRS. The aim of this study was to investigate the therapeutic role of Klotho in CRS after unilateral renal IRI through its anti-inflammatory action. MethodsWe examined renal tissue structure and function, intracellular Ca2+ dynamics in adult ventricular cardiomyocytes and serum cytokine levels from C57BL/6 mice that suffered unilateral renal IRI by occluding the left pedicle for 60 min and reperfusion for 8 days. The animals were treated with recombinant Klotho protein starting from the day of the surgery, then daily for 8 days. ResultsAfter Klotho treatment for 8 days, the left renal tissue remained damaged, however the renal function was restored due to the right kidney tissue preservation. In parallel, Klotho also prevented an increase in serum interleukin (IL-) 6, IL-1β, and tumor necrosis factor alpha (TNF-α) levels. CH and low cell contraction were also prevented, as well as a decrease in systolic Ca2+ transients and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA2a) activity measured as Ca2+ transient decay, an increase in spontaneous Ca2+ release and the incidence of pro-arrhythmic events. ConclusionsThe Klotho treatment showed promise, playing an important role in the pathophysiology of CRS. We were unable to observe a total renoprotective role of the compound in the model; in turn, a cardioprotective role of Klotho was demonstrated through the prevention of hypertrophy and normalization of the Ca2+ cycle dysfunction of cardiomyocytes. We propose that Klotho acts in the cardiorenal syndrome by systematically preventing inflammation and increased FGF23, alleviating cardiac outcomes.