Higher Interleukin-6 Research Articles

Effect of ultrasound-guided stellate ganglion block on lung protection for patients undergoing one-lung ventilation.

To explore the potential effect of ultrasound-guided stellate ganglion block (SGB) on lung protection for patients undergoing one-lung ventilation (OLV). A total of 123 patients undergoing elective one-lung ventilation surgery were selected as research subjects in this prospective study. These patients were randomly divided into the SGB group, control group and blank group on average. Stellate ganglion block was carried out in the SGB and control groups. Patients in the SGB group were injected with 6 ml mixture of 0.25% ropivacaine hydrochloride and 1% lidocaine hydrochloride, while those in the control group were injected with 6 mL of 0.9% saline. Punctures weren't performed for patients in the blank group. The same induction and maintenance of general anesthesia was adopted for all three groups. Hemodynamics, respiratory parameters and arterial blood gas analysis were recorded after entering the operation room (T0), pre-OLV (T1), 30 min after OLV (T2), 60 min after OLV (T3), at the end of surgery (T4), and 30 min after extubation (T5). Oxygenation index (OI), pulmonary shunt fraction (Qs/Qt) and pH value were compared at different time points. Intravenous serum was collected at T0, T3 and T5 for the detection of surfactant proteins A (SP-A), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-6 (IL-6) and interleukin-10 (IL-10) levels, respectively. The complications related to SGB after surgery and the postoperative pulmonary complications within 72 h were recorded. At T1, T2, and T3, MAP level in SGB group was lower than that in blank and control groups (P<0.05). At T2, and T3, SGB group had lower hear rate (HR), peak airway pressure (Ppeak) and tidal volume (TV) than blank and control groups (all P<0.05). From T2 to T5, SGB group had higher OI but lower Qs/Qt than blank and control groups (both P<0.05). At T3 and T5, SGB group had lower SP-A, IL-6, and MDA levels but higher IL-10 and SOD levels than blank and control groups (all P<0.05). There was one case of hypoxemia in the blank group within 72 h after surgery. Ultrasound-guided SGB has lung-protective effects on patients undergoing OLV, which significantly improves patients' OI, reduces intrapulmonary shunts, declines ventilator-induced lung damage, and inhibits inflammatory response as well as oxidative stress (China Clinical Trial Registry, registration number ChiCTR2000033385, https://www.chictr.org.cn).

Fish oil supplementation in obese rats ameliorates metabolic syndrome response.

Accumulation of visceral adipose tissue is associated with metabolic syndrome (MS), insulin resistance, and dyslipidemia. Here we examined several morphometric and biochemical parameters linked to MS in a rodent litter size reduction model, and how a 30-day fish oil (FO) supplementation affected these parameters. On day 3 post-birth, pups were divided into groups of ten or three. On day 22, rats were split into control (C) and small litter (SL) until 60 days old. Then, after metabolic disturbance and obesity were confirmed, FO supplementation started for 30 days and the new groups were named control (C), FO supplemented (FO), obese (Ob), and obese FO supplemented (ObFO). Comparison was performed by Student t-test or 2-way ANOVA followed by Tukey post hoc test. At the end of the 60-day period, SL rats were hyperphagic, obese, hypoinsulinemic, normoglycemic, and had high visceral fat depot and high interleukin (IL)-6 plasma concentration. Obese rats at 90 days of age were fatter, hyperphagic, hyperglycemic, hypertriacylgliceromic, hipoinsulinemic, with low innate immune response. IL-6 production ex vivo was higher, but in plasma it was not different from the control group. FO supplementation brought all biochemical changes to normal values, normalized food intake, and reduced body weight and fat mass in obese rats. The innate immune response was improved but still not as efficient as in lean animals. Our results suggested that as soon MS appears, FO supplementation must be used to ameliorate the morpho- and biochemical effects caused by MS and improve the innate immune response.

Padrão de resistência a antibióticos e características patológicas de Escherichia coli patogênica aviária O78:K80 em galinhas

Avian pathogenic Escherichia coli (APEC) induces colibacillosis, an acute and systemic disease, resulting in substantial economic losses in the poultry sector. This study aimed to investigate the antibiotic resistance pattern associated with frequent virulence gene distribution in APEC O78:K80 that may cause pathological alterations in chickens. The antibiogram profile showed high resistance to erythromycin, chloramphenicol, tetracycline, ampicillin, and co-trimoxazole, followed by intermediate resistance to ciprofloxacin, levofloxacin, enrofloxacin, norfloxacin, nitrofurantoin, and doxycycline hydrochloride, and sensitive to amikacin, streptomycin, gentamicin, and colistin. Virulence gene distribution identifies eight (irp-2, iutA, ompT, iss, iucD, astA, hlyF, iroN) genes through a conventional polymerase chain reaction. APEC O78:K80 caused significantly high liver enzyme concentrations, serum interleukin-6 and tumor necrosis factor-alpha levels in experimental birds. Also, infected birds have hypoproteinemia, hypoalbuminemia, and hyperglobulinemia. Necropsy examination revealed fibrinous perihepatitis and pericarditis, congested lungs, intestinal ecchymotic hemorrhages and necrotizing granulomatosis of the spleen. Histopathological examination depicted hepatocellular degeneration, myocardial necrosis, interstitial nephritis, intestinal hemorrhages and lymphopenia in the spleen. This study is the first evidence to assess the antibiotic resistance profile linked with virulence genes and clinicopathological potential of APEC O78:K80 in chickens in Pakistan, which could be a useful and rapid approach to prevent and control the disease by developing the control strategies.

Impact of sleeve gastrectomy on the periodontal status of patients with and without type 2 diabetes: a 1-year prospective real-world study.

Periodontitis is a chronic inflammatory disease potentially associated with obesity and type 2 diabetes (T2D). Sleeve gastrectomy (SG) has shown substantial effect on weight loss and treatment of T2D. However, there is no direct evidence comparing the impact of SG on the periodontal status of patients with and without T2D. To determine the impact of SG on the periodontal status of patients with and without T2D in a real-world setting. In a prospective and two-armed cohort design, participants who were scheduled for SG at an affiliated hospital between April 2022 and December 2022 were approached for eligibility. After a clinical evaluation and oral examination, those with periodontitis were included and further divided into the DM group (diabetic) and the Control group (non-diabetic) with a 1-year follow-up after surgery. The primary outcome was the periodontal status of patients at 12 months after SG. The secondary outcomes included weight loss, diabetes remission, and alterations in inflammatory markers for up to 1 year after SG. Fifty-seven and 49 patients were included in the DM and the Control group, respectively. Before surgery, patients in the DM group had further worsened periodontal condition compared with those in the Control group. Accompanied by weight loss and glucose reduction, patients in both groups demonstrated significant decreases in plaque index (PLI) and bleeding index (BI) with no alterations in probing depth or clinical attachment loss for up to 1 year after SG. Even patients in the DM group achieved less TWL% (32.79 ± 6.20% vs. 37.95 ± 8.34, P<0.01), their periodontal condition had more substantial improvement with no significant difference in PLI and BI between groups at 1 year after SG. We also observed a significant reduction in the levels of high sensitive C-reactive protein and interleukin-6 in both groups at 1 year after SG. Both patients with and without T2D demonstrated improved periodontal status for up to 1 year after SG. Patients with T2D achieved less weight loss but a more substantial improvement in periodontal condition. The significant reduction in inflammatory biomarkers contributed to the improvement of periodontal status after SG.

Elevated Interleukin-6 (IL-6) Levels with Ig (G &amp; M) Antibodies in the Recovery Phase of Patients with COVID-19: Indication of Cytokine Storm and Re-infection

The innate immune response to coronavirus disease (COVID-19) by inflammatory cytokines, such as interleukin 6 (IL-6), has been described as an early response, followed by an adaptive immune response with the production of antibodies. IL-6 is produced in response to viral infections and is crucial for the activation of T cells and the differentiation of B cells, which produce antibodies. Immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies are produced during the initial acute period of infection and the recovery period from the period of onset of symptoms. There has been some relationship between the innate response of the cytokine and the adaptive response of the antibodies in patients with COVID-19 infection. There has been a positive correlation between IL-6 levels and the presence of COVID-19 antibodies, suggesting that higher IL-6 levels may be associated with a stronger immune response and studies have confirmed that patients with higher IL-6 levels have a higher antibody response. High IL-6 levels on admission observed within 2 weeks after onset of symptoms were positively correlated with high concentrations of IgG seen 5 weeks after onset of symptoms. We have previously described elevated IL-6 levels in the sera of 68% of COVID-19 convalescent patients (40–93 days) post-onset of symptoms (recovery phase). In this study we decided to investigate whether there was some relationship between the IL-6 levels in patients 40–93 days post-onset of symptom in the recovery phase and their antibody response using a wide range of antibody assays (iCHROMA IgG, GOLD IgG &amp; IgM, Abbott SARS-CoV-2 IgG II Quant-test (Abbott S IgG), Diasorin Liaison SARS-CoV-2 S1/2 (Diasorin S1/2 IgG). The patients were divided into two groups, those with normal IL-6 levels (&lt;7 pg/ml) and those with elevated IL-6 levels (&gt;7 pg/ml). All patients (100%) had positive IgG antibodies, only 8 out the 28 patients (29%) were positive for IgM antibodies. The mean antibodies concentrations of the patients (n = 9) with normal IL-6 levels (&lt;7 pg/ml) for iCHROMA IgG (20.0 Units), GOLD IgG (34.4 AU/mL), Abbott IgG (4175 AU/mL), Diasorin Liaison IgG (75.8 AU/mL) and GOLD IgM (4.7 AU/mL), respectively. The mean antibodies concentrations of the patients (n = 19) with elevated IL-6 levels (&gt;7 pg/ml) for iCHROMA IgG (20.9 Units), GOLD IgG, (34.9 AU/mL), Abbott IgG (2287 AU/mL), Diasorin Liaison IgG (121.7 AU/mL) and GOLD IgM (11.2 AU/mL), respectively. The antibodies of the patients with the elevated IL-6 levels were significantly higher for Diasorin Liaison IgG (p = 0.02) and GOLD IgM (p = 0.003) but lower for Abbott IgG (p = 0.02). In conclusion, this study using a panel of antibody assays highlights that increased levels of IL-6 in the convalescent phase (recovery phase) indicate an active immune response leading to higher concentrations of antibodies especially IgM, suggesting that cytokine storms and re-infection occur in the recovery phase.

High interleukin-6 levels induced by COVID-19 pneumonia correlate with increased circulating follicular helper T cell frequency and strong neutralization antibody response in the acute phase of Omicron breakthrough infection.

Acute immune responses to coronavirus disease 2019 (COVID-19) are influenced by variants, vaccination, and clinical severity. Thus, the outcome of these responses may differ between vaccinated and unvaccinated patients and those with and without COVID-19-related pneumonia. In this study, these differences during infection with the Omicron variant were investigated. A total of 67 patients (including 47 vaccinated and 20 unvaccinated patients) who were hospitalized within 5 days after COVID-19 symptom onset were enrolled in this prospective observational study. Serum neutralizing activity was evaluated using a pseudotyped virus assay and serum cytokines and chemokines were measured. Circulating follicular helper T cell (cTfh) frequencies were evaluated using flow cytometry. Twenty-five patients developed COVID-19 pneumonia on hospitalization. Although the neutralizing activities against wild-type and Delta variants were higher in the vaccinated group, those against the Omicron variant as well as the frequency of developing pneumonia were comparable between the vaccinated and unvaccinated groups. IL-6 and CXCL10 levels were higher in patients with pneumonia than in those without it, regardless of their vaccination status. Neutralizing activity against the Omicron variant were higher in vaccinated patients with pneumonia than in those without it. Moreover, a distinctive correlation between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions was observed only in vaccinated patients. The present study demonstrates the existence of a characteristic relationship between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions in Omicron breakthrough infection.

Exploring systemic inflammation in children with chronic kidney disease: correlates of interleukin 6.

Systemic inflammation (SI) is linked to chronic kidney disease (CKD) progression and multiple complications. Data regarding SI biomarkers in pediatric patients are scarce. This case-control and cross-sectional study investigates the correlation of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), total iron binding capacity (TIBC) and serum albumin to serum interleukin-6 (IL-6). NLR and PLR were measured in 53 patients (median age: 12.9years), including 17 on dialysis and 36 with a median glomerular filtration rate of 39ml/min/1.73m2, and in 25 age and sex-matched healthy controls. Iron profile, serum albumin and IL-6 were measured in the patient group. IL-6 levels > 3rd quartile were classified as high. Patients presented higher NLR and PLR and particularly those on dialysis (p < 0.001 and p = 0.001). We observed a significant correlation between natural logarithm (ln) of IL-6 (lnIL-6) and NLR (rs = 0.344, p = 0.014), serum albumin (rs = -0.350, p = 0.011) and TIBC (rs = -0.345, p = 0.012) after adjustment for CKD stage, while the correlation between lnIL-6 and PLR was not significant (rs = 0.206, p = 0.151). Combination of NLR, serum albumin and TIBC predicted high IL-6 (13 patients) with an AUC of 0.771 (95% CI 0.608-0.943). Pairing of NLR ≥ 1.7 and TIBC ≤ 300μg/dL exhibited the highest sensitivity (76.9%), while incorporating serum albumin ≤ 3.8g/dL along with them achieved the highest specificity (95%) for detecting high IL-6 levels. Both NLR and PLR levels increase in CKD, especially in patients on chronic dialysis. NLR, rather than PLR, along with TIBC and serum albumin, are associated with IL-6 in pediatric CKD.

Mesenchymal stem cells overexpressing interleukin-10 prevent allergic airway inflammation

BackgroundsAllergic airway inflammation is prevalent worldwide and imposes a considerable burden on both society and affected individuals. This study aimed to investigate the therapeutic advantages of mesenchymal stem cells (MSCs) overexpressed interleukin-10 (IL-10) for the treatment of allergic airway inflammation, as both IL-10 and MSCs possess immunosuppressive properties.MethodsInduced pluripotent stem cell (iPSC)-derived MSCs were engineered to overexpress IL-10 via lentiviral transfection (designated as IL-10-MSCs). MSCs and IL-10-MSCs were administered intravenously to mice with allergic inflammation induced by ovalbumin (OVA), and the features of allergic inflammation including inflammatory cell infiltration, Th cells in the lungs, and T helper 2 cell (Th2) cytokine levels in bronchoalveolar lavage fluid (BALF) were examined. MSCs and IL-10-MSCs were co-cultured with CD4+ T cells from patients with allergic rhinitis (AR), and the levels of Th2 cells and corresponding type 2 cytokines were studied. RNA-sequence was performed to further investigate the potential effects of MSCs and IL-10-MSCs on CD4+ T cells.ResultsStable IL-10-MSCs were established and characterised by high IL-10 expression. IL-10-MSCs significantly reduced inflammatory cell infiltration and epithelial goblet cell numbers in the lung tissues of mice with allergic airway inflammation. Inflammatory cell and cytokine levels in BALF also decreased after the administration of IL-10-MSCs. Moreover, IL-10-MSCs showed a stronger capacity to inhibit the levels of Th2 after co-cultured with CD4+ T cells from patients with AR. Furthermore, we elucidated lower levels of IL-5 and IL-13 in IL-10-MSCs treated CD4+ T cells, and blockade of IL-10 significantly reversed the inhibitory effects of IL-10-MSCs. We also reported the mRNA profiles of CD4+ T cells treated with IL-10-MSCs and MSCs, in which IL-10 played an important role.ConclusionIL-10-MSCs showed positive effects in the treatment of allergic airway inflammation, providing solid support for the use of genetically engineered MSCs as a potential novel therapy for allergic airway inflammation.

Interleukin-10 disrupts liver repair in acetaminophen-induced acute liver failure.

Systemic levels of the anti-inflammatory cytokine interleukin 10 (IL-10) are highest in acetaminophen (APAP)-induced acute liver failure (ALF) patients with the poorest prognosis. The mechanistic basis for this counterintuitive finding is not known, as induction of IL-10 is hypothesized to temper the pathological effects of immune cell activation. Aberrant production of IL-10 after severe liver injury could conceivably interfere with the beneficial, pro-reparative actions of immune cells, such as monocytes. To test this possibility, we determined whether IL-10 levels are dysregulated in mice with APAP-induced ALF and further evaluated whether aberrant production of IL-10 prevents monocyte recruitment and/or the resolution of necrotic lesions by these cells. Our studies demonstrate that in mice challenged with 300 mg/kg acetaminophen (APAP), a hepatotoxic dose of APAP that fails to produce ALF (i.e., APAP-induced acute liver injury; AALI), Ly6Chi monocytes were recruited to the liver and infiltrated the necrotic lesions by 48 hours coincident with the clearance of dead cell debris. At 72 hours, IL-10 was upregulated, culminating in the resolution of hepatic inflammation. By contrast, in mice treated with 600 mg/kg APAP, a dose that produces clinical features of ALF (i.e., APAP-induced ALF; AALF), IL-10 levels were markedly elevated by 24 hours. Early induction of IL-10 was associated with a reduction in the hepatic numbers of Ly6Chi monocytes resulting in the persistence of dead cell debris. Inhibition of IL-10 in AALF mice, beginning at 24 hours after APAP treatment, increased the hepatic numbers of monocytes which coincided with a reduction in the necrotic area. Moreover, pharmacologic elevation of systemic IL-10 levels in AALI mice reduced hepatic myeloid cell numbers and increased the area of necrosis. Collectively, these results indicate that during ALF, aberrant production of IL-10 disrupts the hepatic recruitment of monocytes, which prevents the clearance of dead cell debris. These are the first studies to document a mechanistic basis for the link between high IL-10 levels and poor outcome in patients with ALF.

Relationship between serum interleukin-6 levels and severity of coronary artery disease undergoing percutaneous coronary intervention

BackgroundCytokines play a potential role in atherosclerosis pathogenesis and progression. We investigated the association of interleukin-6 (IL-6) with the angiographic severity of coronary artery disease (CAD).MethodsThree hundred ten angiografically diagnosed CAD patients and 210 controls were enrolled in this study. CAD patients were stratified according to IL-6 cut-off value into high levels IL-6 group (≥ 9.5 pg/mL) and low levels IL-6 group (< 9.5 pg/mL). The severity of CAD was assessed according to Gensini score (GS), artery stenosis degree and the number of vessels involved. The mean age was 60.3 ± 11.0 years.ResultsThe level of IL-6 in patients was increased compared to controls and ranged from 1.5 to 3640.0 pg/mL. High levels of IL-6 were significantly associated with high levels of GS (> 40) but not with stenosis degree and vessel score. GS levels were significantly more elevated in patients with high levels of IL-6 group than in low IL6 levels patients (60.6 ± 39.5 vs 46.7 ± 37.2; p = 0.027). The analysis of the ROC curve performed in myocardial infarction patients showed that IL-6 (AUC: 0.941 (CI 95% 0.886, 0.997; p < 0.001) could be a powerful predictor marker in evaluating the infarct size after myocardial infarction when compared to myonecrosis biomarkers.ConclusionsIL-6 levels were associated with the severity of CAD assessed by the GS. Based on the highest levels of IL-6 measured in patients with STEMI, our study strongly suggests that IL-6 could be a powerful marker in evaluating the myocardial necrosis.Trial registrationClinicalTrials.gov Number: NCT03075566 (09/03/2017).

Increased Bone Turnover and Decreased BCMA Levels in Patients with Response to Anti-BCMA CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma

Introduction For most patients (pts), multiple myeloma (MM) remains an incurable disease. Osteolytic lesions (OL) are present in 80% of pts at diagnosis and skeletal-related events are the most common cause for symptomatic relapse. Hence, myeloma bone disease (MBD) is a major cause of morbidity and mortality especially among pts with relapsed/refractory MM (RRMM). B cell maturation antigen (BCMA) targeted chimeric antigen receptor (CAR) T cells have revolutionized treatment of patients with RRMM. While remission rates are high and pts experience long-standing treatment free intervals after CAR T cell treatment, little is known about its effects on MBD and bone turnover. The latter can be determined in plasma by measuring markers of bone formation and resorption. We aimed to analyze the longitudinal development of bone turnover during and after anti-BCMA CAR T cell treatment in RRMM pts. Methods We analyzed 28 consecutive pts with RRMM who underwent treatment with either Idecabtagene-Vicleucel (n=27) or Ciltacabtagen-Autoleucel (n=1) at our center between December 2021 and February 2023. Median age at infusion was 63 (range 39-75) years. 57% of pts were male. All pts were triple-class exposed, 21% had penta-class refractory disease. Status prior to CAR T cell infusion was complete remission (CR, 11%), partial remission (PR, 21%), very good PR (14%), stable disease (4%), or progressive disease (PD, 50%). The impact of CAR T cell treatment on bone turnover was assessed by collecting plasma samples on the day of T cell apheresis, as well as days (d) 30 and 100 after CAR T cell infusion. Samples were analyzed by ELISA to evaluate plasma levels of bone formation marker Osteocalcin (OCN), bone resorption markers Tartrate-resistant acid phosphatase 5b (TRAcP5b) and fibroblast growth factor 23 (FGF23) as well as BCMA as a marker for the targeted myeloma cells. Median levels were compared between subgroups by Wilcoxon tests. Remission status after CAR T cell therapy was first evaluated at d 30 according to International Myeloma Working Group consensus criteria. Median follow-up was 6 months. Results Of the 28 pts treated with anti-BCMA CAR T cells, 64% achieved at least a PR (responders), while 36% had PD shortly (30 d) after. Within 14 d after infusion, 82% developed a cytokine release syndrome (CRS, °I or II), in 30% of which Tocilizumab was applied. Only 1 pt developed immune effector cell-associated neurotoxicity syndrome. In responders, BCMA levels in plasma decreased significantly between apheresis and d 30 ( P&amp;lt;.01) and between apheresis and d 100 ( P&amp;lt;.01), while pts with PD showed no significant change in BCMA levels at the same timepoints ( P=.6 and P=.8). Furthermore, BCMA levels were significantly higher in pts with PD at d 30 ( P&amp;lt;.01) and d 100 ( P=.02), compared to responders (Figure 1). Regarding bone resorption markers, TRAcP5b levels were significantly increased in responders ( P=.01) but not pts with PD ( P=.56) on d 30 after apheresis. Furthermore, we determined a significant increase of intact FGF23 between apheresis and d 30 ( P&amp;lt;.01) and a subsequent significant decrease of intact FGF23 ( P=.02) between d 30 and d 100 in responders. Since FGF23 and interleukin-6 (IL-6) are physiologically dependent, the observed FGF23 dynamics are likely to be an effect of increasing IL-6 in the context of CRS. Aptly, pts who received Tocilizumab because of full-blown CRS had higher intact FGF23 levels at d 30 ( P=.02) compared to pts without Tocilizumab treatment. The bone formation marker OCN showed a significant increase in responders between apheresis and d 100 ( P=.01), as well as between d30 and d100 ( P=.02), while there were no significant changes in OCN levels over the time in pts with PD (Figure 2). Conclusion Pts responding to treatment with anti-BCMA CAR T cells, showed an increased bone turnover shortly after infusion. The increase of bone resorption marker levels appeared to be a short-term trend and could possibly be related to inflammation and high interleukin levels during the first days after infusion. However, we also saw a steady increase of bone formation marker OCN, which remained significant till d 100 in responders. Our data implies, that response to anti-BCMA CAR T cells is accompanied by increasing bone formation. Further analyses are needed to evaluate, whether this treatment can have positive long-term effects on MBD.

Macrophage-hitchhiking interleukin-10 plasmid DNA delivery system modulates rheumatoid arthritis microenvironment via the re-polarization of macrophages

Rheumatoid arthritis (RA) is a common chronic inflammatory disease and the current treatments for RA are unsatisfactory due to the buffer barrier from the RA microenvironment. Interleukin-10 (IL-10) was found to be able to modulate rheumatoid arthritis microenvironment (RAM) by the metabolic reprogramming of macrophages. However, its clinical application has proven challenging mainly due to its short half-life, non-ideal targeting efficiency via systemic administration and poor tissue penetration. Taking advantage of the recruitment of macrophages, we constructed an innovative macrophage-hitchhiking IL-10 pDNA delivery system using the peptides bearing nuclear localization signal (NLS) and tuftsin-modified disulfide-crosslinked polymers (bPEI-SS-PEG-T) which was responsive to the intracellular glutathione concentration. Firstly, we formed NLS/DNA complexes via electrostatic interactions to enhance the nuclear entry efficiency. Then NLS/DNA complexes were combined with bPEI-SS-PEG-T to construct bPEI-SS-PEG-T/NLS/DNA NPs with sizes of 168.4 nm and zeta potentials of + 10.9 mV. As the bPEI-SS-PEG-T was biodegradable and the tuftsin peptides enhanced macrophage-mediated phagocytosis, the nanoparticles exhibited lower cytotoxicity and better cellular uptake in addition to higher nuclear entry efficiency, leading to better IL-10 plasmid transfection. In addition, these macrophage-hitchhiking nanoparticles could effectively accumulate at inflammatory sites of RA via intra-peritoneal injection due to the macrophage migration to the inflammatory joints and alleviate symptoms of inflammation in vivo by inducing the re-polarization of macrophages, which might be mediated by the inhibition of mammalian target of rapamycin (mTOR) and the induction of arginase-2 (Arg2). As a result, this macrophage-hitchhiking gene delivery system demonstrated excellent inflammation targeting ability, good nuclear entry ability, high IL-10 plasmid transfection efficiency and great therapeutic efficacy in vivo, which is promising for the treatment of rheumatoid arthritis. Besides, this delivery system also provides a novel strategy for the gene therapy and the gene delivery system design for rheumatoid arthritis and other similar inflammatory diseases from the perspective of the inflammatory microenvironment.

Circulating cytokines and alcoholic liver disease: a two-sample bidirectional Mendelian randomization study

Background Increased inflammation in the liver during ethanol exposure is a major feature of alcoholic liver disease (ALD). An important contributing component to the development of ALD is the inflammatory response brought on by immunological response, however the connection between individual circulating cytokines and ALD is still unclear. To ascertain the causation, we conducted a two-sample bidirectional Mendelian randomization research. Methods We extracted 41 cytokines and growth factors of 8293 Europeans and ALD cases of the same ethnicity (1416 cases and 217,376 controls) from the Genome-Wide Association Studies (GWAS) database for two-sample bidirectional MR analysis. Results Our analyses suggest that higher interleukin-7 (IL-7) levels are associated with an increased risk of ALD (p = 0.028, OR = 1.191,95% CI = 1.019–1.392), while tumor necrosis factor related apoptosis inducing ligand (TRAIL) is a protective factor for ALD (p = 0.032, OR = 0.863, 95% CI = 0.754–0.988) which can reduce the risk of disease occurrence. In addition, genetically predicted ALD does not affect the expression of circulating cytokines regulators. Conclusions Our study supports that cytokines play a pivotal role in the pathogenesis of ALD. To determine the mechanisms and pathways of action of these biomarkers, further basic research is required to ensure their clinical suitability for preventing and treating ALD.

Interleukin-6 and disease activity in childhood systemic lupus erythematosus

Background Systemic lupus erythematosus (SLE) is a complex disease with various manifestations. Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities which plays an important role in immune regulation and inflammation. Serum level of IL-6 may be used as a parameter of disease activity, especially in pediatric SLE patients with mild disease activity or total remission with conflicting clinical manifestations and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores.&#x0D; Objective To identify the characteristics of serum IL-6 concentration in pediatric SLE with mild disease activities and total remission.&#x0D; Methods This case-control study was performed at the allergy-immunology outpatient clinic, Department of Child Health Dr. Cipto Mangunkusumo Hospital, Jakarta and Dr. Sardjito Hospital, Yogyakarta. Serum IL-6 concentration and disease activity were assessed in all pediatric SLE patients aged 1-18 years old. Disease activity was assessed with SLEDAI scores and serum level of IL-6 was measured by enzyme-linked immunosorbent assay.&#x0D; Results Among 60 subjects included in this study, 30 subjects with mild activities were in the case group and 30 subjects with total remissions were in the control group. There was no difference in serum IL-6 concentration between the case and control group (OR 0.483; 95%CI 0.041to 5.628; P=0.500). In this study, 2 subjects with urinary tract infection had high serum IL-6 concentrations.&#x0D; Conclusion There is no difference in serum IL-6 concentration between pediatric SLE patients with mild disease activities compared to total remissions.

Early and Timely Use of Hemofiltration Therapy with Poly Methyl Meth Acrylate (PMMA) Filters in Severe COVID-19 Adult Respiratory Distress Syndrome Patients: A Single Centre Study in India

A high Interleukin-6 (IL-6) level in COVID-19 plays a major role in the pathophysiology and is considered a reliable parameter in predicting the adversity of the disease. In COVID-19. Extracorporeal blood purification has been proposed as an adjuvant therapy and it aims at controlling the dysregulation in the immune system. Essentially, it lowers the upregulated levels of several mediators and therefore controls the cytokine storm, instead of actively targeting individual pathways of inflammation. Positive IL-6 balance post-Polymethyl methacrylate (PMMA) filter used for Cytokine storm in COVID-19 patients with dialysis has shown to be an independent predictor of mortality. A retrospective analysis of seventeen patients wherein hemofiltration was used for cytokine storm with dialysis, sepsis, and septic shock. The inflammatory markers post-hemofiltration sessions were supervised to understand hemofiltration's efficacy. The average age of the patients was 70.2 (18.2) years. They were classified as responders or non-responder groups based on the decrease or no change/ increase respectively between the pre-and post-filtration IL-6 levels. A 3.6-fold increase was noticed in non-responders (N=11) for IL-6 levels post hemofiltration. Responders demonstrated a 21.4% (p&lt;0.05) reduction in IL-6 levels post hemofiltration. Of these, 4 who survived demonstrated a decrease in IL-6 levels of 66.2%. Of 10 non-responders, none survived. However, the survival rate was 71.43 percent among the responders. There was a significant statistical difference in the mortality rate between the two groups (p= 0.003).Cytokine storm, an overwhelming immunological response in COVID-19 patients, can be controlled successfully by the early and timely use of hemofiltration therapy with PMMA filters like Hemofeel. However, patients with higher positive IL-6 balance post-hemofiltration may be associated with limited outcomes.

The Clinical Relevance of Selected Cytokines in Newly Diagnosed Multiple Myeloma Patients.

Multiple myeloma (MM) is the second most common hematological neoplasm. Cytokines, chemokines, and their receptors, induced by the microenvironment of MM, participate in tumor growth, the attraction of leukocytes, cell homing, and bone destruction. This study aimed to assess the correlation between the pretreatment serum concentrations of interleukin-6 (IL-6), interleukin-8 (IL-8), angiogenic chemokine monocyte chemoattractant protein-1 (MCP-1), and vascular endothelial growth factor (VEGF) and the clinical outcomes and survival of patients newly diagnosed with MM. The study group consisted of 82 individuals. The IL-8 concentration was significantly positively correlated with the age of onset (p = 0.007), the International Staging System (ISS) stage (p = 0.03), the Eastern Cooperative Oncology Group (ECOG) performance status (p < 0.001), the degree of anemia before treatment (p < 0.0001), the degree of kidney disease (p < 0.001), and VEGF (p = 0.0364). Chemotherapy responders had significantly lower concentrations of IL-8 (p < 0.001), IL-6 (p < 0.001), and VEGF (p = 0.04) compared with non-responders. Patients with treatment-induced polyneuropathy had significantly higher levels of IL-8 (p = 0.033). Patients with a high level of IL-6 had a 2-fold higher risk of progression-free survival (PFS) reduction (17 vs. 35 months; HR = 1.89; p = 0.0078), and a more than 2.5-fold higher risk of overall survival (OS) reduction (28 vs. 78 months; HR = 2.62; p < 0.001). High levels of IL-6, IL-8, and VEGF demonstrated significant predictive values for some clinical conditions or outcomes of newly diagnosed MM patients. Patients with an early response to chemotherapy had a significantly lower concentration of these cytokines. A high pretreatment IL-6 concentration was an independent negative prognostic marker for newly diagnosed MM patients.

Cardiovascular and inflammatory biomarkers for non-invasive detection of coronary artery obstruction and prediction of long-term survival in patients with suspected chronic coronary syndrome

Abstract Introduction and methods: The knowledge about diagnostic and prognostic value of cardiac and inflammatory biomarkers in patients with chronic coronary syndrome (CCS) is limited. To address this, we analyzed serum levels of selected biomarkers in 2536 patients with suspected CCS (35% female) from the Leipzig LIFE Heart Study who were admitted for coronary angiography. The median follow-up was 10 years. The following biomarkers were considered: high sensitive troponin T (hsTNT), N-terminal pro B-type natriuretic peptide (NT-proBNP), copeptin, high sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6). Patients were stratified according to the angiographic severity of coronary artery disease (CAD): CAD0 (no sclerosis), CAD1 (non-obstructive, i.e., stenosis &amp;lt; 50%), CAD2 (≥ one stenosis ≥ 50%). Group comparison (GC) included GC1: CAD0 + 1 vs. CAD2, GC2: CAD0 vs. CAD1 + 2. Using age-, sex and symptom-based pre-test probability (PTP) table for obstructive CAD (i.e. CAD 2) which was published in the current CCS guidelines, patients were further classified into the following three categories: PTP &amp;lt; 5% (n=559), PTP 5-15% (n=545) and PTP &amp;gt; 15% (n=1432). Results CAD0, CAD1, CAD2 were apparent in 999, 529, and 1008 patients, respectively. Upon adjustment for traditional risk factors (TRF) the levels of hsTNT, NT-proBNP and IL-6 showed significant difference in GC1 (hsTNT: p=2.0x10-10, NT-proBNP: p=0.049, IL6: p=0.030). In GC2 only elevated hsTNT remained significant (p=1.9x10-7). In the ROC analysis only hsTNT slightly improved the AUC for the GC1-comparison in addition to TRF (0.729 with vs 0.712 witt hsTNT, p=0.013). Within the PTP subcategories the following results were obtained: PTP &amp;lt; 5%: AUC 0.747 with vs 0.730 without hsTNT, p=0.017; PTP 5-15 %: AUC 0.636 with vs 0.670 without hsTNT, p&amp;lt;0.001; PTP &amp;gt; 15%: AUC 0.699 with vs 0.677 without hsTNT, p= 0.024). In PTP 5-15% subgroup TropT cut-off value &amp;lt; 3 pg/mL (N= 119 / 23.4%) showed sensitivity of 89.7% and specificity of 73.1% for CAD2 detection. Ten years survival in groups CAD0, CAD1, CAD2 were 88.3%, 77.3%, 72.4%, respectively. In the multivariate analysis elevated hsTNT, NT-proBNP, copeptin and IL-6 remained significant mortality predictors in CAD2 patients with hazard ratios of similar magnitude (i.e. 1.5, 1.3, 1.4 and 1.3 per unit on the log-scale of the parameters, respectively). hsCRP did not reach significance. In the model stratified into tertiles according to the effects of classical risk factors and the joint biomarker levels for except hsCRP, hazard rates were 3.13 (tertile 2 vs 1) and 11.2 (tertile 3 vs 1). Conclusions In the present study hsTNT substantially improved the detection of obstructive CAD particularly in patients with intermediate PTP 5-15%. Furthermore, the studied biomarkers enable fast and precise non-invasive prediction of mortality risk in patients with suspected CCS, allowing tailored primary and secondary CAD prevention in this high-risk group.

Hemodynamics and plasma biomarkers in individuals with mild-to-moderate ascending aortic dilatation and tricuspid aortic valves

Abstract Background Ascending aortic (AA) dilatation is a silent disease that requires frequent follow-up measurements of the AA diameter. Unfortunately, the AA diameter is an insufficient predictor of future growth and complications. Hemodynamic and circulating biomarkers represent promising ways of improving the risk stratification in AA dilatation. Most patients with AA dilatation have tricuspid aortic valves (TAV). However, previous studies have mainly focused on AA dilation in individuals with bicuspid aortic valves (BAV) using either hemodynamic or circulating biomarkers separately. Purpose To assess the relationship between hemodynamics in the AA and circulating biomarkers in individuals with mild-to-moderate AA dilatation and age-and-sex matched controls with TAV. Methods The study cohort of individuals with mild-to-moderate AA dilatation were identified based on AA diameter on coronary CT angiography in the population-based Swedish CardioPulmonary BioImage Study (SCAPIS) in Linköping. 54 cases with AA diameter &amp;gt;= 40 mm and 50 controls with AA diameter &amp;lt;40 mm (mean age 59, 19% female) underwent 4D Flow cardiovascular magnetic resonance imaging (CMR). The 4D Flow CMR images were processed to compute mean and maximum velocities, wall shear stress (WSS), flow displacement (FD) at peak systole, and oscillatory shear index (OSI) in the AA. Markers of collagen synthesis and degradation; type I collagen α1 chain (COL1α1), matrix metalloproteinase (MMP)-1,-2,-3,-9,-12) and their inhibitors (TIMP-1,-2,-3,-4), were quantified in plasma (n=104). High sensitivity C-reactive protein and interleukin(IL)-6 were used to assess systemic inflammation. Results FD at the location of maximum dilatation, mean FD and mean OSI were higher in cases compared to controls. Mean velocity, mean WSS and maximum WSS were lower in cases compared to controls. None of the circulating biomarkers differed significantly between cases and controls. Interestingly, several circulating biomarkers correlated with hemodynamics markers in the whole cohort. COL1α1, MMP-2 and TIMP-2 correlated inversely with max OSI (r=-0.342, p=0.001; r=-0.277, p=0.006; r=-0.238, p=0.018, respectively) while MMP-3 correlated positively with mean velocity (r=0.274, p=0.006), mean WSS (r=0.270, p=0.007), max WSS (r=0.220, p=0.029), and inversely with FD at the location of maximum dilatation (r=-0.218, p=0.031). TIMP-4 correlated with mean OSI (r=-0.284, p=0.005). Conclusions Several hemodynamic markers obtained with 4D Flow CMR were altered in mild-to-moderate AA dilatation with TAV, while circulating biomarkers did not differ from controls. However, significant correlations were identified between several biomarkers and hemodynamic markers. We therefore speculate that the levels of circulating biomarkers may be altered as the disease progresses. Future studies should examine the implications of these novel findings along the trajectory of AA dilation and its association with complication risk.Methods figureHemodynamics markers table

Salivary Interleukin-1 Levels in Oral Squamous Cell Carcinoma: A Case-Control Study.

Oral squamous cell carcinoma (OSCC) is a prevalent malignancy with a significant impact on global health. The identification of non-invasive biomarkers for early detection and monitoring of OSCC remains crucial. A total of 100 subjects, comprising 50 patients with histopathologically confirmed OSCC and 50 age- and sex-matched healthy controls, were enrolled in the study. Salivary samples were collected from all participants and analyzed using enzyme-linked immunosorbent assays (ELISA) to measure IL-1 levels. Clinical data, including demographic information, smoking habits, and alcohol consumption, were obtained from patient records. The mean salivary IL-1 level was significantly higher in OSCC patients compared to healthy controls (P < 0.001). Furthermore, subgroup analysis demonstrated that advanced stages of OSCC correlated with significantly elevated IL-1 levels when compared to early-stage OSCC (P < 0.05). Additionally, high salivary IL-1 levels were associated with a more aggressive tumor phenotype and poorer prognosis, as reflected by tumor size, lymph node metastasis, and overall survival (P < 0.01). This case-control study provides compelling evidence that salivary Interleukin-1 (IL-1) levels are significantly elevated in patients with OSCC.

Modulation of inflammatory, oxidative, and apoptotic stresses mediates the renoprotective effect of daidzein against glycerol-induced acute kidney injury in rats.

Acute kidney injury (AKI) is a life-threatening complication that accompanies rhabdomyolysis. Daidzein is a dietary isoflavone that has various biological activities. This study examined the therapeutic potential of daidzein and the underlying mechanisms against AKI induced by glycerol in male rats. Animals were injected once with glycerol (50%, 10 ml/kg, intramuscular) for induction of AKI and pre-treated orally with daidzein (25, 50, and 100 mg/kg) for 2 weeks. Biochemical, histopathological, immunohistopathological, and molecular parameters were assessed to evaluate the effect of daidzein. The results revealed that the model group displayed remarkable functional, molecular, and structural changes in the kidney. However, pre-administration of daidzein markedly decreased the kidney relative weight as well as the levels of urea, creatinine, K, P, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and cystatin C. Further, daidzein lessened the rhabdomyolysis-related markers [lactate dehydrogenase (LDH) and creatine kinase (CK)]. Notably, the enhancement of the antioxidant biomarkers [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and reduced glutathione (GSH) is accompanied by a decrease in malondialdehyde (MDA) and nitric oxide (NO) levels. Moreover, upregulated gene expression levels of nuclear factor erythroid 2-related factor 2 (Nfe212) and hemeoxygenase-1 (Hmox1) were exerted by daidzein administration. Rats who received daidzein displayed markedly lower interleukin-1β (IL-1β), tumor nuclear factor-α (TNF-α), myleoperoxidase (MPO), and nuclear factor kappa B (NF-κB) levels together with higher interleukin-10 (IL-10) related to the model group. Remarkably, significant declines were noticed in the pro-apoptotic (Bax and caspase-3) and rises in antiapoptotic (Bcl-2) levels in the group that received daidzein. The renal histological screening validated the aforementioned biochemical and molecular alterations. Our findings support daidzein as a potential therapeutic approach against AKI-induced renal injury via suppression of muscle degradation, oxidative damage, cytokine release, and apoptosis.