Plasma Levels Of Interleukin-6 Research Articles

Noncontact 3D Bioprinting of Proteinaceous Microarrays for Highly Sensitive Immunofluorescence Detection within Clinical Samples.

Immunofluorescence assays are extensively used for the detection of disease-associated biomarkers within patient samples for direct diagnosis. Unfortunately, these 2D microarrays suffer from low repeatability and fail to attain the low limits of detection (LODs) required to accurately discern disease progression for clinical monitoring. While three-dimensional microarrays with increased biorecognition molecule density stand to circumvent these limitations, their viscous component materials are not compatible with current microarray fabrication protocols. Herein, we introduce a platform for 3D microarray bioprinting, wherein a two-step printing approach enables the high-throughput fabrication of immunosorbent hydrogels. The hydrogels are composed entirely of cross-linked proteins decorated with clinically relevant capture antibodies. Compared to two-dimensional microarrays, these proteinaceous microarrays offer 3-fold increases in signal intensity. When tested with clinically relevant biomarkers, ultrasensitive single-plex and multiplex detection of interleukin-6 (LOD 0.3 pg/mL) and tumor necrosis factor receptor 1 (LOD 1 pg/mL) is observed. When challenged with clinical samples, these hydrogel microarrays consistently discern elevated levels of interleukin-6 in blood plasma derived from patients with systemic blood infections. Given their easy-to-implement, high-throughput fabrication, and ultrasensitive detection, these three-dimensional microarrays will enable better clinical monitoring of disease progression, yielding improved patient outcomes.

Inflammatory Cytokines and Cognition in Alzheimer's Disease and Its Prodrome.

The aim of this study was to investigate the association between blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals. Peripheral concentration of TNF-α and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed. The 37 participants included 8 patients with Alzheimer's disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-α and IL-6 levels were higher in patients with AD than in healthy controls. TNF-α levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-α and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-α level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-α level and the z-score on Word List Learning remained significant when age was adjusted. The difference in the blood levels of TNF-α and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-α levels were associated with worse immediate memory performance, even after adjusting for age.

Complement activation and lung injury in Japanese patients with COVID-19: a prospective observational study

Background The production of inflammatory cytokines is reportedly increased in patients with coronavirus disease 2019 (COVID-19), causing the migration of neutrophils and monocytes to lung tissues. This disrupts the air–blood barrier by damaging the bronchial epithelial and vascular endothelial cells. As multiorgan dysfunction in sepsis is considered to be partly caused by complement activation, which can cause lung injury in patients with COVID-19. There are limited studies examining the link between complement activation in patients with COVID-19. This study aimed to AQinvestigate the association of complement activation with the pathophysiology of COVID-19. Twenty-seven patients with COVID-19 were enrolled in this study and classified into two groups depending on the indication for mechanical ventilation. Plasma complement factors (C3a, C5a, Ba, and sC5b-9), complement regulators (sCD59 and factor H), interleukin-6 (IL-6), and syndecan-1 levels were measured using Enzyme-linked immunosorbent assay (ELISA). Results: All complement factors and regulators, IL-6, and syndecan-1 levels were significantly elevated in patients with COVID-19 compared with those in healthy controls. C5a and sC5b-9 levels were decreased significantly in the invasive mechanical ventilation (IMV) group compared with those in the non-IMV group. Syndecan-1 levels were significantly increased in the IMV group compared with those in the non-IMV group. Conclusions: Complement activation is an exacerbating factor for lung injury in patients with COVID-19. Complement factors are nonessential predictors of mechanical ventilation; however, syndecan-1 could be a biomarker of COVID-19 severity in patients.

Association between overweight and central interleukin-6 in a nonclinical adult population.

Overweight is associated with low-grade systemic inflammation. However, its effect on neuroinflammation remains unclear. We examined the possible association between overweight and neuroinflammation using cerebrospinal fluid (CSF) in a nonclinical adult population in Japan. CSF and plasma levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), plasma levels of C-reactive protein (CRP), and leptin were measured in nonclinical adult participants (35 males and 34 females) who had no current or past history of neuropsychiatric diseases. We performed partial correlation analyses with sex and age as covariates between the body mass index (BMI) and the inflammatory markers and compared them between overweight and nonoverweight participants. The BMI significantly correlated with CSF levels of IL-6 (rs = 0.32, p = 0.009), plasma levels of CRP (rs = 0.30, p = 0.016), IL-1β (rs = 0.29, p = 0.019), IL-6 (rs = 0.25, p = 0.042), TNF-α (rs = 0.43, p < 0.001), and leptin (rs = 0.72, p < 0.001). Overweight participants (BMI ≧ 25) had significantly higher CSF levels of IL-6 (p < 0.001), plasma levels of IL-1β (p = 0.023), TNF-α (p < 0.001), and leptin (p < 0.001) than the nonoverweight participants. Overweight is associated with central IL-6, a marker for neuroinflammation, as well as systemic inflammation markers, even in a nonclinical population.

Inflammatory cytokines, cortisol, and anhedonia in patients with treatment-resistant depression after consecutive infusions of low-dose esketamine.

Anhedonia, defined as a significant loss of interest or pleasure, is one of the core symptoms of treatment- resistant depression (TRD) and is often associated with poor prognosis. This article primarily investigates the changes in anhedonia symptoms, inflammatory markers, and cortisol levels in TRD patients after low-dose esketamine treatments. A total of sixty patients with TRD were enrolled in the clinical study of esketamine. We primarily assessed the severity of depressive symptoms and anhedonia using the Hamilton Rating Scale for Depression (HAMD) and the Snaith-Hamilton Pleasure Scal(SHAPS), respectively, before esketamine treatment and within 24h after each treatment. Blood specimens were collected before the first treatment and within 1h after the sixth treatment, measuring the levels of cortisol, interleukin-6(IL-6), interleukin-4(IL-4), and tumor necrosis factor-alpha(TNF-α) in plasma. We found that after six consecutive infusions of low-dose esketamine, patients' depressive symptoms and anhedonia showed improvement. After six treatments, plasma levels of cortisol, IL-6, and TNF-α decreased in patients with TRD, while the anti-inflammatory cytokine IL-4 increased. Multiple linear regression analysis revealed that baseline cortisol levels were correlated with anhedonia, while inflammatory factors showed no significant correlation. Add-on esketamine appears to be a good choice for the treament of the anhedonia in TRD. It has also shown promising effects on altering inflammatory markers in patients with TRD. Moreover, elevated plasma cortisol levels may serve as a potential biomarker for anhedonia in patients with TRD.

Possible association of elevated CSF IL-6 levels with anxiety and frustration in psychiatric disorders.

Neuroinflammation is an important causal factor for a variety of psychiatric disorders. We previously reported increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and major depressive disorder. The present study aimed to examine the possible association of interleukin-6 levels with anxiety and frustration, negative valence symptoms shared in various psychiatric disorders. We included 129 patients with psychiatric disorders and 70 controls. CSF and plasma interleukin-6 levels were measured by immunoassay kits, and psychological symptoms were assessed with the State-Trait Anxiety Inventory, and the Basic Psychological Need Satisfaction and Frustration Scale. To examine regional cerebral blood flow, patients underwent arterial spin labeling analysis using magnetic resonance imaging. Cerebrospinal fluid interleukin-6 levels were significantly correlated with State-Trait Anxiety Inventory-trait anxiety (r = 0.25, P = 0.046) and Basic Psychological Need Satisfaction and Frustration Scale-autonomy frustration scores (r = 0.29, P = 0.018). Patients with abnormally high cerebrospinal fluid interleukin-6 levels (defined >97.5 percentile of the controls) had higher scores for trait anxiety (P = 0.035) and autonomy frustration (P = 0.026), and significantly increased regional cerebral blood flow in the left superior temporal gyrus, bilateral nucleus accumbens, and cerebellum than the remaining patients. Patients with elevated cerebrospinal fluid interleukin-6 constitute a subpopulation of psychiatric disorders associated with anxiety and autonomy frustration, which may be related to altered functions in specific brain areas.

Abstract B044: Durable T-cell-mediated anti-tumor immune response to pancreatic cancer cells overexpressing interleukin 6

Abstract Tumor immune resistance contributes to low survivorship in patients with pancreatic ductal adenocarcinoma (PDAC). To understand how tumor-secreted factors might impact anti-tumor immunity, we developed a model of PDAC tumor overexpressing interleukin-6 (IL-6), a known driver of pancreatic tumorigenesis and cancer cachexia, in orthotopically implanted PDAC cancer cells (OT-PDACIL6). This model utilized codon-optimized IL6 to accurately detect tumor cells in the pancreas and distal organs via qPCR. OT-PDACIL6 tumors developed poorly- differentiated, infiltrative carcinomas, which were histologically similar to the PDAC cell line they were derived from (OT-PDACparental). Surprisingly, OT-PDACIL6 tumors were present at 5 days post implantation, but undetectable by histology or qPCR by 10 days post implantation. OT- PDACIL6 and sham mouse survival were equivalent (87.5%) at 76 days post-implantation. OT- PDACparental mortality was 100% at day 13. We concluded that OT-PDACIL6 tumors resolve spontaneously. IL-6 is well-established as a driver of cachexia, and we saw that OT-PDACIL6 tumors induced a rapid cachexia phenotype that began to resolve as the tumor was cleared. Plasma IL-6 levels tracked with tumor burden. At 5 days, plasma IL-6 was 100-fold higher in OT-PDACIL6 mice than in OT-PDACparental mice, but undetectable in OT-PDACIL6 mice after 12 days. We hypothesized that high levels of IL-6 were driving an anti-tumor immune response. To assess changes in tumor immune infiltrate that could lead to tumor clearance, we measured a broad range of immune cells using flow cytometry and immunofluorescent histology. At peak tumor burden, we observed exacerbated splenomegaly, and increased tumor-infiltrating T cells and NK cells in OT-PDACIL6 mice. T regulatory cells were decreased in OT-PDACIL6 tumors. CD4/CD8 antibody-based depletion prevented tumor clearance and significantly decreased survival of OT-PDACIL6 mice, indicating that T cells are necessary for IL-6-driven PDAC tumor clearance. We then tested whether the anti-tumor T cell response was durable using a secondary tumor challenge with PDACparental cells. This revealed that the anti-tumor T cell response elicited by mice bearing OT-PDACIL6 tumors was sufficient to prevent development of OT-PDACparental tumors, likely due to induction of long-term memory T cells during the initial tumor challenge. We assessed the effect of the anti-tumor immune response on metastases and found that PDACIL6 cells were detected by qPCR in lungs of 58% of mice at day 5, and not detected at day 12. We conclude that extremely high levels of tumor-derived IL-6 are sufficient to drive an anti-tumor T cell response that rapidly and durably clears the tumor. The combination of increased tumor-infiltrating T cells and decreased T regulatory cells are likely both important aspects of the immune response observed in OT-PDACIL6 mice. This surprising finding highlights the pleiotropic effects of IL-6, which is known to promote tumorigenesis and cachexia, and yet, in this work, is the driving force underlying tumor clearance. Citation Format: Paige C Arneson-Wissink, Alexandra Q Bartlett, Heike Mendez, Xinxia Zhu, Jessica Dickie, Matthew McWhorter, Peter R Levasseur, Parham Diba, Katelyn T Byrne, Gregory D Scott, Robert Eil, Aaron J Grossberg. Durable T-cell-mediated anti-tumor immune response to pancreatic cancer cells overexpressing interleukin 6 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B044.

Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption

Human immunodeficiency virus (HIV) persistence during antiretroviral therapy (ART) is associated with heightened plasma interleukin-10 (IL-10) levels and PD-1 expression. We hypothesized that IL-10 and PD-1 blockade would lead to control of viral rebound following analytical treatment interruption (ATI). Twenty-eight ART-treated, simian immunodeficiency virus (SIV)mac239-infected rhesus macaques (RMs) were treated with anti-IL-10, anti-IL-10 plus anti-PD-1 (combo) or vehicle. ART was interrupted 12 weeks after introduction of immunotherapy. Durable control of viral rebound was observed in nine out of ten combo-treated RMs for >24 weeks post-ATI. Induction of inflammatory cytokines, proliferation of effector CD8+ T cells in lymph nodes and reduced expression of BCL-2 in CD4+ T cells pre-ATI predicted control of viral rebound. Twenty-four weeks post-ATI, lower viral load was associated with higher frequencies of memory T cells expressing TCF-1 and of SIV-specific CD4+ and CD8+ T cells in blood and lymph nodes of combo-treated RMs. These results map a path to achieve long-lasting control of HIV and/or SIV following discontinuation of ART.

Alpha B-crystallin Ameliorates Imbalance of Redox Homeostasis, Inflammation and Apoptosis in an Acute Lung Injury Model with Rats.

Ischemia-reperfusion (IR) of the aorta is a significant contributor to the development of postoperative acute lung damage after abdominal aortic surgery. The aim of the present study was to examine the effect of alpha B-crystallin, a small heat shock protein (known as HspB5), on lung injury induced by abdominal aortic IR in rats. Male Sprague-Dawley rats were divided into three groups: control, ischemia-reperfusion (IR, 90 min ischemia and 180 min reperfusion), and alpha B-crystallin +IR. Alpha B-crystallin (50 μg/100 g) was intraperitoneally administered 1 h before IR. Lung tissue samples were obtained for histological and biochemical analyses of oxidative stress and cytokine and apoptosis parameters in plasma, lung tissues, and bronchoalveolar lavage (BAL) fluid. The levels of malondialdehyde, reactive oxygen species, total oxidant status, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), nuclear factor kappa B (NFKβ), caspase-9 (CASP-9), 8-hydroxy-2'-deoxyguanosine, total antioxidant status, superoxide dismutase, and interleukin-10 levels in lung tissues, plasma, and BAL fluid (p<0.05 versus control) increased in Aortic IR. However, alpha B-crystallin significantly reduced the lung tissue levels of oxidative, inflamatuvar, and apoptotic parameters in the plasma, lung tissues, and BAL fluid (p<0.05 versus aortic IR). Histopathological results showed that alpha B-crystallin ameliorated the morphological changes related to lung injury (p<0.001). Alpha B-crystallin substantially restored disrupted the redox balance, inflammation, and apoptotic parameters in rats exposed to IR. The cytoprotective effect of alpha B-crystallin on redox balance might be attributed to improved lung injury.

Effects of Melatonin on Exercise-Induced Oxidative Stress in Adults with Obesity Undergoing a Multidisciplinary Body Weight Reduction Program.

Background: Obesity is characterized by increased oxidative stress, which, in a vicious circle, promotes chronic low-grade inflammation. Melatonin, a well-documented antioxidant, might be useful as a supplement to enhance the cardiometabolic benefits of any body weight reduction program (BWRP). Objectives/Methods: The present study aimed to evaluate the post-exercise oxidative stress and inflammation in a group of subjects with obesity treated with melatonin (2 mg/die) or placebo, undergoing a 2-week BWRP, with the administration of a single bout of acute exercise at the start and the end of the protocol (G1-G15). Results: Eighteen adults with obesity were enrolled and distributed to the two arms of the study: the melatonin group (F/M: 7/2; age: 27.8 ± 5.6 years; body mass index [BMI]: 43.0 ± 4.9 kg/m2) and the placebo group (F/M: 6/3; age: 28.8 ± 5.0 years; BMI: 42.8 ± 4.0 kg/m2). BWRP induced a decrease in BMI and waist circumference (WC) in both groups; plasma glucose, blood glycated hemoglobin (HbA1c), and neutrophil to lymphocyte ratio (NLR) were reduced only in the placebo group. Importantly, plasma biological antioxidant potential (BAP) increased throughout BWRP. Paradoxically, melatonin enhanced post-exercise production of plasma derivatives of reactive oxygen metabolites (d-ROMs) and erythrocytic glutathionyl-Hb (HbSSG) (at G1 and G15). Finally, differently from the placebo group, melatonin-treated subjects did not exhibit the BWRP-induced decrease in plasma levels of interleukin-6 (IL-6), before and after exercise, at the end of two weeks (G15). Conclusions: Melatonin is presumably an antioxidant with "conditional" prooxidant actions. The use of melatonin as a supplement in subjects with obesity might be deleterious due to the abolishment of BWRP-induced cardiometabolic benefits.

Simultaneous removal of endotoxins, inflammatory mediators and uremic toxins in ICU patients with septic shock: a retrospective cohort study

Sepsis, one of the leading causes of death, is still lacking specific treatment. OXIRIS (BAXTER, Deerfield, IL, USA) is the first device allowing combined removal of endotoxins, inflammatory mediators and uremic toxins, alongside fluid balance control. Available data is very limited. This retrospective propensity score-matched cohort study of adult patients with septic shock aimed to evaluate septic shock duration and mortality in patients treated with either standard of care renal replacement therapy (RRT) or RRT with combined hemoadsorption, who were admitted to the interdisciplinary surgical intensive care unit at Heidelberg University Hospital during the years 2018 through 2021. Main outcomes were duration of shock, thirty-day mortality and plasma interleukin-6 levels before and after initiation of hemoadsorption. Included were 117 patients (female, 33%; male 67%); median age: 67 (16) years. After matching: 42 patients (female, 33%; male, 67%); mean age: 59.1 ± 13.8 years. There was no statistically significant difference in septic shock duration (p = 0.94; hazard ratio (HR) 0.97 (95% CI, 0.48–1.97)). Thirty-day survival analysis showed a non-statistically significant survival difference. (p = 0.063; HR 0.43 (95% CI, 0.17–1.09)). A post-hoc 90-day survival analysis revealed statistically significant longer survival and lower death hazard ratio in patients treated with RRT + HA (p = 0.037; HR = 0.42 (95% CI, 0.18–0.99). In conclusion, RRT with combined hemoadsorption of endotoxins, inflammatory mediators and uremic toxins is a modality worth further investigation.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients.

Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury (ALI) and multiple organ dysfunction syndrome (MODS). Interleukin 6 (IL-6) is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications. To investigate the relationship among plasma IL-6 levels, risk of ALI, and disease severity in critically ill patients with sepsis. This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022. A total of 83 septic patients were enrolled. Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay. The development of ALI and MODS was monitored during hospitalization. Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores. Among the 83 patients with sepsis, 38 (45.8%) developed ALI and 29 (34.9%) developed MODS. Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI (median: 125.6 pg/mL vs 48.3 pg/mL; P < 0.001). Similarly, patients with MODS had higher IL-6 levels than those without MODS (median: 142.9 pg/mL vs 58.7 pg/mL; P < 0.001). Plasma IL-6 levels were strongly and positively correlated with APACHE II (r = 0.72; P < 0.001) and SOFA scores (r = 0.68; P < 0.001). Elevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI and MODS. Higher IL-6 levels were correlated with greater disease severity, as reflected by higher APACHE II and SOFA scores. These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI and disease severity in patients with sepsis.

Assessing the impact of opioid-free anesthesia using the modified Mulimix technique on postoperative pain in bariatric surgery patients: a correlative randomized double-blinded trial

Background &amp; objective: The effective management of postoperative pain in bariatric surgery poses significant challenges to the anesthesiologists and the surgeons. Opioids have been the mainstay of postoperative pain management; but recently, opioid-free anesthesia (OFA) has been a popular option in an effort to prevent the opioid related side-effects. The objective of this study was to assess the effects of OFA utilizing the modified mulimix technique on the levels of plasma interleukin-2 (IL-2) and interleukin-6 (IL-6). In addition, the study aimed to evaluate the duration of analgesia and the analgesic requirements during the first 24 hours postoperatively. Methodology: A total of 60 patients were randomly assigned to the OFA Group, which received opioid-free anesthesia, and the OBA Group, which received Opioid-Based Anesthesia. The modified Mulimix technique was used in both groups. Serum samples were collected from all patients during skin incision and after the surgical procedure. Subsequently, these samples were assessed for IL-2 and IL-6 levels. The postoperative analgesic consumption was compared in both groups. Results: Regarding serum IL-2 and IL-6 levels in the two study groups, there was a statistically significant difference after the conclusion of surgery, and the skin incision was made. Regarding the initial rescue analgesia postoperatively assessment, the OBA group demonstrated a substantially greater overall consumption of analgesics within the first 24 h. The study revealed a significant difference in VAS values between the OBA Group and the OFA Group at 2 h, 4 h, and 6 h postoperatively. Conclusion: The modified mulimix technique effectively reduces postoperative plasma inflammatory mediators, interleukin-2 and interleukin-6, and results in decreased postoperative pain, thus reducing the postoperative analgesia consumption Abbreviations: OBA - Opioid based anesthesia; OFA - opioid-free anesthesia; IL-2 - interleukin-2; IL-6 - interleukin-6; VAS - visual analogue scale Keywords: Bariatric surgery, interleukin, Mulimix, opioid, pain, immunological response. Citation: Seyam SHA, Hassan AE, Elsayed MM. Assessing the impact of opioid-free anesthesia using the modified Mulimix technique on postoperative pain in bariatric surgery patients: a correlative randomized double-blinded trial. Anaesth. pain intensive care 2024;28(4):721−726; DOI: 10.35975/apic.v28i4.2516 Received: March 04, 2024; Reviewed: May 18, 2024; Accepted: May 19, 2024

Perioperative Changes in Plasma Nitrite and IL-6 Levels Predict Postoperative Atrial Fibrillation (POAF) and Acute Kidney Injury (AKI) after Cardiac Surgery.

Background: Postoperative atrial fibrillation (POAF) and acute kidney injury (AKI) are common yet significant complications after cardiac surgery, with incidences of up to 40% for each. Here, we assessed plasma nitrite and serum interleukin-6 (IL-6) levels before and after cardiac surgery to quantify the extent to which oxidative stress and inflammation contribute to POAF and AKI occurrence. Methods: We prospectively enrolled 206 cardiac surgical patients. Plasma nitrite and serum IL-6 levels were determined preoperatively and at 24 h, 48 h and 72 h postoperatively. The patients had continuous EKG monitoring for occurrence of POAF, while daily serum creatinine was measured for determination of stage 1 + AKI. Results: Postoperatively, 78 (38%) patients experienced AF, and 47 (23%) patients experienced stage 1 + AKI. POAF analysis: Age, ACE-inhibitor use, valve surgery and percent change in baseline plasma nitrite at 24 h postoperatively were associated with POAF in multiple logistic regression analysis. The inclusion of this new biomarker significantly improved the POAF prediction model (AUC 0.77 for clinical risk factors alone, to AUC 0.81). AKI analysis: A history of diabetes mellitus was associated with AKI in multiple logistic regression analysis, and the addition of preoperative IL-6 levels improved the prediction model for AKI occurrence (AUC 0.69 to AUC 0.74). Conclusions: We previously observed selective upregulation of NADPH oxidase isoform 4 (NOX4) in patients with AF, a critical causal role of NOX4 for AF in zebrafish and a robust inhibitory effect of nitric oxide (NO) on NOX4. Our data innovatively demonstrate that a reduction in circulating nitrite levels, likely implicative of elevated NOX4-mediated oxidative stress, independently associates with POAF and improves POAF prediction, whereas the inclusion of circulating IL-6 levels improves the prediction model for AKI. Therefore, therapeutic strategies to mitigate these pathophysiological sequalae of surgical stress may reduce the incidence of severe postoperative complications of POAF and AKI.

Effect of Zinc and Vitamin E on Blood Testosterone and Inflammatory Markers in Male Patients Undergoing Heart Surgery

Background: Zinc and vitamin E affect the metabolism of testosterone and inflammatory factors. We aimed to evaluate the effect of zinc and vitamin E supplementation on plasma testosterone levels and inflammatory markers in patients undergoing coronary artery bypass graft (CABG) surgery. Methods: This study was a secondary analysis of a previously published randomized controlled trial in a subsample of male patients undergoing CABG surgery. Patients in the zinc-vitamin E group (n = 27) received oral zinc (120 mg) and vitamin E (1200 international units) one day prior to surgery, followed by 30 mg of zinc and 200 units of vitamin E per day for three weeks after surgery. Patients in the control group (n = 25) received a placebo. Plasma levels of total testosterone, cortisol, interleukin-6 (IL-6), and white blood cell toll-like receptor-4 (TLR-4) gene expression were determined at three-day and three-week intervals following surgery. Changes in these markers were analyzed using a repeated-measures analysis of variance. Results: A comparison of the groups revealed no significant difference in the concentration of plasma total testosterone levels (P = 0.059) or cortisol. Three weeks following the surgical procedure, a positive correlation was observed between the change in plasma zinc concentrations and the change in plasma testosterone levels (r = 0.32; P = 0.025). The administration of zinc and vitamin E supplements resulted in a reduction in plasma IL-6 levels on postoperative day 3 (P = 0.025), while no significant effect was observed in week 3 (P = 0.091). The expression of the TLR-4 gene in WBCs was found to be lower in the zinc-vitamin E group compared to the placebo group on day 3 (P = 0.051) and week 3 (P = 0.025). Conclusions: The administration of zinc and vitamin E to patients undergoing CABG was associated with a relative improvement in postoperative inflammatory markers. Plasma zinc levels demonstrated a correlation with testosterone levels, suggesting a potential avenue for further research in these patients.

Interleukin-6 positively correlates with cardiovascular disease predictor algorithms and biomarker in rheumatoid arthritis patients.

Chronic inflammation is believed as the main culprit of the link between cardiovascular disease (CVD) and rheumatoid arthritis (RA). Interleukin-6 (IL-6) is a pro-inflammatory cytokine with a key role in RA pathophysiology and also correlates with joint destruction and disease activity. This study evaluates the association between IL-6 plasma level and cardiac biomarker NT-proBNP, HS-CRP, CVD predictor algorithms, Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE), as well as with CXCL9 and its receptor, CXCR3 in RA patients compared to the controls. Sixty RA patients (30 early and 30 late) and 30 healthy persons were included in this study. IL-6 and NT-proBNP plasma levels were measured by the ELISA. Also, HS-CRP plasma levels were quantified using the immunoturbidimetric assay. The CVD risk was assessed by the FRS and SCORE. IL-6 plasma levels were significantly higher in the early and late RA patients compared to the controls (p < 0.001). There was a positive correlation between IL-6 with DAS-28 (p = 0.007, r = 0.346), BPS (p = 0.002, r = 0.396), BPD (p = 0.046, r = 0.259), SCORE (p < 0.001, r = 0.472), and FRS (p < 0.001, r = 0.553), and a negative association with HDL (p = 0.037, r = -0.270), in the patients. Also, IL-6 plasma level positively correlated with HS-CRP (p = 0.021, r = 0.297) and NT-proBNP (p = 0.045, r = 0.260) in the patients. Furthermore, a positive association was found between IL-6 plasma levels and CXCL9 (p = 0.002, r = 0.386), and CXCR3 (p = 0.018, r = 0.304) in the patients. Given the interesting association between IL-6 with various variables of CVD, IL-6 may be considered a biomarker for assessing the risk for future cardiovascular events in RA patients.

The efficacy of levosimendan and dobutamine on reducing peripheral blood interleukin-6 levels and improving cardiac function in patients with septic cardiomyopathy: a comparative study.

In patients with severe septic cardiomyopathy, levosimendan has been found to improve myocardial contractility more effectively than dobutamine, although the underlying mechanisms remain unclear. This study aims to compare the effects of levosimendan and dobutamine on cardiac function and inflammatory markers in patients with septic cardiomyopathy, and to further investigate the advantages and disadvantages of both treatments. We included 40 patients with septic cardiomyopathy treated in the intensive care unit of our hospital from September 2020 to September 2023. The patients were randomly divided into a levosimendan group (n=20) and a dobutamine group (n=20). Plasma concentrations of interleukin-6 (IL-6), interleukin-1beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) were measured by immunofluorescence at the start of treatment, 24 hours, and 48 hours. Cardiac troponin I (cTnI) concentrations were determined by chemiluminescence, and left ventricular ejection fraction (LVEF) was measured using the Simpson method. After 24 hours of treatment, there were no significant differences in IL-6, IL-1β, and TNFα levels between the two groups (P>0.05). However, at 48 hours, the IL-6 level in the levosimendan group was significantly lower than that in the dobutamine group (319.43±226.05 pg/ml vs. 504.57±315.20 pg/ml, P=0.039), while IL-1β and TNF-α levels showed no significant differences (P>0.05). Additionally, the cTnI level in the levosimendan group was significantly lower than that in the dobutamine group (1.01±0.54 ng/ml vs. 1.40±0.63 ng/ml, P=0.042), and LVEF was significantly higher in the levosimendan group (50.60±6.11% vs. 46.90±4.95%, P=0.042). These findings suggest that levosimendan may reduce plasma IL-6 levels, alleviate myocardial injury, and improve myocardial contractility in patients with septic cardiomyopathy compared to dobutamine.

Biopsy Proteome Score Performs Well as an Effect Measure in a Gluten Challenge Trial of Celiac Disease

Background and aimsDevelopment of novel treatments for celiac disease (CeD) is dependent on precise tools to monitor changes in gluten-induced mucosal damage. Current histology measures are subjective and difficult to standardize. Biopsy proteome scoring is an objective alternative to histology which is based on robust changes in biological pathways that directly reflect gluten-induced mucosal damage. In this study we aimed to evaluate biopsy proteome scoring as an effect measure in a clinical trial setting by measuring intestinal remodeling in response to oral gluten challenge. MethodsWe analyzed biopsies from a 14-day gluten challenge trial of treated CeD patients that consumed 3 g (n = 6) or 10 g (n = 7) gluten per day. Sections from individually embedded biopsies collected before and after challenge were processed for proteome scoring (n = 109) and measurement of villous height to crypt depth (Vh:Cd) ratio (n = 58). Proteome scores were compared to histology, intraepithelial lymphocyte (IEL) frequency and plasma interleukin-2 (IL-2). ResultsChange in proteome scores were significant for the group of patients who consumed 10 g gluten, but not for the group who consumed 3 g gluten. Altogether, 8 of 13 patients had changes in delta proteome scores above cut-off. Proteome scores correlated with Vh:Cd ratios both at run-in and at day 15. Proteome scores at day 15 correlated with IEL frequency and with plasma IL-2 levels measured 4 hours post gluten intake. ConclusionBiopsy proteome scoring is a simple and reliable measure of gluten-induced mucosal remodeling in response to 14-day oral gluten challenge (ClinicalTrials.gov, number NCT03409796).

Exploring the correlation between childhood trauma experiences, inflammation, and brain activity in first-episode, drug-naive major depressive disorder.

Childhood trauma experiences and inflammation are pivotal factors in the onset and perpetuation of major depressive disorder (MDD). However, research on brain mechanisms linking childhood trauma experiences and inflammation to depression remains insufficient and inconclusive. Resting-state fMRI scans were performed on fifty-six first-episode, drug-naive MDD patients and sixty healthy controls (HCs). A whole-brain functional network was constructed by thresholding 246 brain regions, and connectivity and network properties were calculated. Plasma interleukin-6 (IL-6) levels were assessed using enzyme-linked immunosorbent assays in MDD patients, and childhood trauma experiences were evaluated through the Childhood Trauma Questionnaire (CTQ). Negative correlations were observed between CTQ total (r = -0.28, p = 0.047), emotional neglect (r = -0.286, p = 0.042) scores, as well as plasma IL-6 levels (r = -0.294, p = 0.036), with mean decreased functional connectivity (FC) in MDD patients. Additionally, physical abuse exhibited a positive correlation with the nodal clustering coefficient of the left thalamus in patients (r = 0.306, p = 0.029). Exploratory analysis indicated negative correlations between CTQ total and emotional neglect scores and mean decreased FC in MDD patients with lower plasma IL-6 levels (n = 28), while these correlations were nonsignificant in MDD patients with higher plasma IL-6 levels (n = 28). This finding enhances our understanding of the correlation between childhood trauma experiences, inflammation, and brain activity in MDD, suggesting potential variations in their underlying pathophysiological mechanisms.

Sustained gut dysbiosis and intestinal inflammation show correlation with weight gain in person with chronic HIV infection on antiretroviral therapy

BackgroundPerson with human immunodeficiency virus type-1 (PWH) are prone to chronic inflammation due to residual viral production, even with antiretroviral therapy (ART), which increases the risk of age-related diseases. There is also limited information on changes in the intestinal environment of PWH during ART. In this longitudinal study, we investigated changes in the gut microbiota, persistence of chronic inflammation, interactions between the gut environment and inflammation, and metabolic changes in PWH using long-term ART.ResultsWe analyzed changes in clinical parameters and gut microbiota in 46 PWH over a mean period of 4 years to understand the influence of gut dysbiosis on inflammation. Overall, changes in the gut microbiota included a decrease in some bacteria, mainly involved in short-chain fatty acid (SCFA) production, and an increase in certain opportunistic bacteria. Throughout the study period, an increase in bacterial-specific metabolic activity was observed in the intestinal environment. Continued decline in certain bacteria belonging to the Clostridia class and metabolic changes in gut bacteria involved in glucose metabolism. Additionally, patients with a low abundance of Parabacteroides exhibited low bacterial alpha diversity and a significant increase in body mass index (BMI) during the study period. Monocyte chemoattractant protein 1, a marker of macrophage activation in the plasma, continued to increase from baseline (first stool collection timepoint) to follow-up (second stool collection timepoint), demonstrating a mild correlation with BMI. Elevated BMI was mild to moderately correlated with elevated levels of plasma interleukin 16 and chemokine ligand 13, both of which may play a role in intestinal inflammation and bacterial translocation within the gut microbiota. The rate of BMI increase correlated with the rate of decrease in certain SCFA-producing bacteria, such as Anaerostipes and Coprococcus 3.ConclusionOur data suggest that despite effective ART, PWH with chronic inflammation exhibit persistent dysbiosis associated with gut inflammation, resulting in a transition to an intestinal environment with metabolic consequences. Moreover, the loss of certain bacteria such as Parabacteroides in PWH correlates with weight gain and may contribute to the development of metabolic diseases.