Elevated Interleukin-6 Levels Research Articles

Potential role of IGF-1R in the interaction between orbital fibroblasts and B lymphocytes: an implication for B lymphocyte depletion in the active inflammatory phase of thyroid-associated ophthalmopathy

BackgroundThyroid eye disease (TED) is an inflammatory process involving lymphocyte-mediated immune response and orbital tissue damage. The anti-insulin-like growth factor-1 receptor (IGF-1R) antibodies produced by B lymphocytes are involved in the activation of orbital fibroblasts and the inflammatory process of orbital tissue damage in TED. The purpose of this study was to explore the role of IGF-1R in the mechanistic connection between orbital fibroblasts and B lymphocytes in TED.MethodsOrbital fibroblasts sampled from orbital connective tissues and peripheral B lymphocytes isolated from peripheral blood, which were obtained from 15 patients with TED and 15 control patients, were co-cultured at a ratio of 1:20. The level of IGF-1R expression in orbital fibroblasts was evaluated by flow cytometry and confocal microscopy. Transient B lymphocyte depletion was induced with anti-CD20 monoclonal antibody rituximab, while the IGF-1R pathway was blocked by the IGF-1R binding protein. The expression levels of interleukin-6 (IL-6) and regulated upon activation, normal T cell expressed and secreted (RANTES) in the co-culture model were quantified via ELISA.ResultsIGF-1R expression was significantly elevated in TED orbital fibroblasts compared to that of controls. A 24-h co-culture of orbital fibroblasts with peripheral B lymphocytes induced elevated expression levels of IL-6 and RANTES in each group (TED patients and controls), with the highest levels occurring in TED patients (T + T group). Rituximab and IGF-1R binding protein significantly inhibited increased levels of IL-6 and RANTES in the co-culture model of TED patients.ConclusionsIGF-1R may mediate interaction between orbital fibroblasts and peripheral B lymphocytes; thus, blocking IGF-1R may reduce the local inflammatory response in TED. Rituximab-mediated B lymphocyte depletion played a role in inhibiting inflammatory responses in this in vitro co-culture model, providing a theoretical basis for the clinical application of anti-CD20 monoclonal antibodies in TED.

N,N-Diarylsulfonamide Reduces Proinflammatory Cytokine Interleukin-6 Levels in Cells through Nuclear Factor-κB Regulation.

The arylsulfonamides were synthesized from aryl sulfonyl chloride and aromatic amines in dichloromethane in the presence of pyridine. The aryne chemistry was used to prepare diarylsulfonamide from arylsulfonamides and O-silylaryl triflate with CsF in acetonitrile at room temperature for 30 min. The synthesized compounds were evaluated for cytotoxicity followed by the cytokine/inflammatory marker's inhibition capability and its mechanism of action in RAW-264.7 cells. Elevated interleukin-6 (IL-6) levels have been reported in inflammatory conditions and inflammation-associated disorders. Hence, reducing the IL-6 levels in inflammatory conditions can serve as an attractive therapeutic target in dealing the inflammation. Among 42 compounds, seven compounds showed significant inhibition of IL-6 levels in lipopolysaccharide (LPS) challenged RAW-264.7 cells at 12.5 μM concentration. Further, investigation revealed that the IC50 value of these compounds for reducing IL-6 levels was found to be in the range of 2.6 to 9.7 μM. The promising compounds 5y (IC50 of 2.6 μM) and 5n (IC50 of 4.1 μM) along with other derivatives fulfil drug-likeness parameters laid down by Lipinski's rule of five. Further, RT-qPCR and Western-blot analysis revealed that treatment with 5n significantly reduced the expression of pro-inflammatory, inflammatory and macrophage marker's expression (IL-1β, CCL2, COX2 and CD68) compared to LPS control. The mechanistic evaluation showed that 5n exhibited anti-inflammatory properties by modulating the nuclear factor-κB (NF-κB) activation. The identified compound can be a promising candidate for further discovery efforts to generate a preclinical candidate effective in inflammation.

Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratio predicting hospital length of stay and mortality in young COVID-19 patients: A retrospective study

Background This study investigated the utility of platelet-to-lymphocyte ratio (PLR) and Neutrophil-to-Lymphocyte ratio (NLR) in patients with COVID-19 with respect to age, early (a week) vs. delayed recovery (> a week) and mortality. Methods This was a retrospective study including 1,016 COVID-19 patients. The discriminatory power and multivariate logistic regression analysis were performed. Results The mean age of patients was 45 (± 13.9), and 75.7% were males. Older patients had elevated NLR, PLR, D-dimer, CRP, and Interleukin-6 levels and longer hospital stay than the younger group (p < 0.001). In-hospital mortality was higher in older adults (26.9% vs. 6.6%, p =0.001). On-admission NLR (5.8 vs. 3.2; P= 0.001) and PLR (253.9±221.1 vs. 192.2±158.5; p = 0.004) were higher in the non-survivors than survivors. Both PLR and NLR displayed significant discriminatory ability for mortality. NLR had a higher AUC and specificity, while PLR exhibited slightly higher sensitivity. In individuals aged ≤55, NLR showed superior discrimination (AUC=0.717) compared to PLR (AUC=0.620). Conversely, for older adults, PLR displayed enhanced discrimination (AUC=0.710), while NLR showed AUC=0.693. Conclusion Higher admission NLR and PLR levels were associated with delayed recovery, whereas an enhanced NLR was associated with considerably higher mortality in older COVID-19 patients.

A real-world study was conducted to develop a nomogram that predicts the occurrence of anastomotic leakage in patients with esophageal cancer following esophagectomy.

The incidence of anastomotic leakage (AL) following esophagectomy is regarded as a noteworthy complication. There is a need for biomarkers to facilitate early diagnosis of AL in high-risk esophageal cancer (EC) patients, thereby minimizing its morbidity and mortality. We assessed the predictive abilities of inflammatory biomarkers for AL in patients after esophagectomy. In order to ascertain the predictive efficacy of biomarkers for AL, Receiver Operating Characteristic (ROC) curves were generated. Furthermore, univariate, LASSO, and multivariate logistic regression analyses were conducted to discern the risk factors associated with AL. Based on these identified risk factors, a diagnostic nomogram model was formulated and subsequently assessed for its predictive performance. Among the 438 patients diagnosed with EC, a total of 25 patients encountered AL. Notably, elevated levels of interleukin-6 (IL-6), IL-10, C-reactive protein (CRP), and procalcitonin (PCT) were observed in the AL group as compared to the non-AL group, demonstrating statistical significance. Particularly, IL-6 exhibited the highest predictive capacity for early postoperative AL, exhibiting a sensitivity of 92.00% and specificity of 61.02% at a cut-off value of 132.13 pg/ml. Univariate, LASSO, and multivariate logistic regression analyses revealed that fasting blood glucose ≥7.0mmol/L and heightened levels of IL-10, IL-6, CRP, and PCT were associated with an augmented risk of AL. Consequently, a nomogram model was formulated based on the results of multivariate logistic analyses. The diagnostic nomogram model displayed a robust discriminatory ability in predicting AL, as indicated by a C-Index value of 0.940. Moreover, the decision curve analysis provided further evidence supporting the clinical utility of this diagnostic nomogram model. This predictive instrument can serve as a valuable resource for clinicians, empowering them to make informed clinical judgments aimed at averting the onset of AL.

Longitudinal Study on Salivary IL-6 Trajectories in Postoperative OSCC Patients After Chemotherapy and Radiotherapy

BackgroundOral squamous cell carcinoma (OSCC) poses a significant healthcare challenge globally, necessitating precise biomarkers for effective management. Interleukin-6 (IL-6) in saliva has emerged as a potential biomarker, yet its dynamics post-chemotherapy and radiotherapy remain underexplored. AimThe aim of our study is to investigate the longitudinal dynamics of salivary interleukin-6 (IL-6) expression in postoperative OSCC patients over a one-year follow-up period after chemotherapy and radiotherapy. MethodsThis longitudinal study enrolled 60 participants, including postoperative OSCC patients and controls, collecting saliva samples over one year. RT-PCR and ELISA techniques measured IL-6 expression. Statistical analyses, including repeated measures ANOVA and univariate tests, evaluated IL-6 dynamics. ResultsPre-treatment, OSCC patients exhibited elevated IL-6 levels compared to controls. Post-therapy, IL-6 levels decreased significantly with p<0.0001, indicating treatment response and further result to baseline normalizing at 6-month follow-up. Significant differences were observed across treatment stages, supporting IL-6 as a diagnostic and prognostic marker for OSCC. RT-PCR and ELISA results showed the statistical significance of IL-6′s role as a predictive marker. ConclusionSalivary IL-6 emerges as a promising biomarker in OSCC management, necessitating further research to harness its diagnostic and therapeutic potential. By understanding IL-6 dynamics, personalized treatment approaches can be developed to improve patient outcomes. Longitudinal studies with larger cohorts and multi-omics approaches are warranted to validate findings and identify novel therapeutic targets.

Correlation between the elevated level of interleukin-6 following actemra administration and the mortality rate of seven severe COVID-19 patients

The escalation and involvement of Interleukin 6 (IL-6) in the pathogenesis of COVID-19 have been documented in numerous studies and are recognized as a diagnostic criterion, disease biomarker, and therapeutic objective. Our study aims to explore the correlation between the elevated level of IL-6 following actemra administration and the mortality rate of seven severe COVID-19 patients who were admitted to the special care department of Ardabil city hospital. In this case-series study, 7 patients with severe COVID-19 were admitted to the special care department of Ardabil city hospital were included in the study. Venous blood samples (3 cc) were taken in admission and after actemra injection. The demographic characteristics of the patients, including age, sex, duration of hospitalization, need for intubation, BMI, and interleukin 6 levels, were recorded in a checklist. The patients were then monitored for their clinical course, disease outcome, and complications. The mean IL-6 before and after actemra was 413.57±138.38 and 805.50±128.18, respectively and the difference was significant. After treatment by actemra, 71.4% of patients were discharged from hospital without mortality. Although elevated IL-6 levels have been associated with cytokine storms and unfavorable consequences in COVID-19 patients. This report indicates that high interleukin levels do not guarantee mortality. Young individuals without underlying conditions were ultimately discharged from the ICU despite severe inflammation, thanks to timely treatment and albeit with severe disability.

Post-COVID syndrome in patients with type 2 diabetes: definition, epidemiology, pathophysiology, biomarkers and genetic associations

The article presents the modern ideas about post-COVID syndrome, indicates various types and classifications of post-COVID syndrome, provides epidemiological data, including the patients with type 2 diabetes, also the definition of post-COVID syndrome is given. The group of patients defined as patients with post-COVID syndrome is very heterogeneous. Post-COVID syndrome is more common in the elderly, with comorbid pathology, severe disease. The pathophysiology of this syndrome in patients with type 2 diabetes mellitus is analyzed, and risk factors are indicated. The main biomarkers of disorders were determined: monocytes and their coefficients, acute phase proteins, some biochemical indicators, including analysis of genetic associations with the severity of post-COVID disorders (interferon gamma gene, methylenetetrahydrofolate reductase gene, ACE2 inhibitor). Genotyping of a sample of 26 single nucleotide polymorphisms in genes implicated in viral entry, immune response, and inflammation were significantly associated not only with the risk of long-term COVID-19 symptoms, but also with the cumulative incidence of post-COVID syndrome. Elevated levels of interleukin 6, C-reactive protein and tumor necrosis factor alpha may serve as potential diagnostic biomarkers in long-term COVID biomarkers of blood vascular transformation have great potential for diagnosis, and angiogenesis modulators may have therapeutic efficacy It has been shown that the vast majority of patients, in particular those suffering from type 2 diabetes, develop post-COVID-19 syndrome, and taking into account pre-existing diseases, post-COVID syndrome is not so harmless. By identifying common biomarkers and genetic associations, it is possible to identify the common molecular mechanism of post-COVID syndrome COVID-19 and diabetes mellitus. The novelty of disease association studies in the context of COVID-19 provides new insights into the management of rapidly evolving long-term COVID and post-COVID syndromes that have significant global implications.

Involvement of necroptotic cell death in macrophages in progression of bleomycin and LPS-induced acute exacerbation of idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is the severe form of interstitial pneumonias. Acute exacerbation (AE) of IPF is characterized by progressive lung fibrosis with the irreversible lung function decline and inflammation, and is often fatal with poor prognosis. However, the physiological and molecular mechanisms in AE of IPF are still not fully understood. In this study, we investigated the mechanism underlying AE of IPF, using bleomycin (BLM) and lipopolysaccharide (LPS) (BLM+LPS)-treated mice. The mice were treated with a single dose of 1.5 mg/kg BLM (on day 0) and/or 0.5 mg/kg LPS (on day 14), and maintained for another 7 days (total 21 days). Administration of BLM+LPS more severely aggravated the respiratory function, fibrosis, and inflammation in the lungs, together with the elevated interleukin-6 level in bronchoalveolar lavage fluid, than the control or BLM alone-treated mice. Moreover, the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay demonstrated that subsequent treatment with LPS elevated cell death in the lungs of BLM-administered mice. Furthermore, the expression levels of mixed lineage kinase domain-like protein (MLKL), a marker of necroptotic cell death, and CD68-positive macrophages were increased, and most of them were co-stained in the lungs of BLM+LPS-treated mice. These results, taken together, indicate that BLM+LPS treatment showed more exacerbated the respiratory function with extensive fibrosis and inflammation than treatment with BLM alone in mice. Fibrosis and inflammation in AE of IPF seen in BLM+LPS-administered mice included an increase in macrophages and their necroptotic cell death.

Constitutive knockout of interleukin-6 ameliorates memory deficits and entorhinal astrocytosis in the MRL/lpr mouse model of neuropsychiatric lupus.

Neuropsychiatric lupus (NPSLE) describes the cognitive, memory, and affective emotional burdens faced by many lupus patients. While NPSLE's pathogenesis has not been fully elucidated, clinical imaging studies and cerebrospinal fluid (CSF) findings, namely elevated interleukin-6 (IL-6) levels, point to ongoing neuroinflammation in affected patients. Not only linked to systemic autoimmunity, IL-6 can also activate neurotoxic glial cells the brain. A prior pre-clinical study demonstrated that IL-6 can acutely induce a loss of sucrose preference; the present study sought to assess the necessity of chronic IL-6 exposure in the NPSLE-like disease of MRL/lpr lupus mice. We quantified 1308 proteins in individual serum or pooled CSF samples from MRL/lpr and control MRL/mpj mice using protein microarrays. Serum IL-6 levels were plotted against characteristic NPSLE neurobehavioral deficits. Next, IL-6 knockout MRL/lpr (IL-6 KO; n = 15) and IL-6 wildtype MRL/lpr mice (IL-6 WT; n = 15) underwent behavioral testing, focusing on murine correlates of learning and memory deficits, depression, and anxiety. Using qPCR, we quantified the expression of inflammatory genes in the cortex and hippocampus of MRL/lpr IL-6 KO and WT mice. Immunofluorescent staining was performed to quantify numbers of microglia (Iba1 +) and astrocytes (GFAP +) in multiple cortical regions, the hippocampus, and the amygdala. MRL/lpr CSF analyses revealed increases in IL-17, MCP-1, TNF-α, and IL-6 (a priori p-value < 0.1). Serum levels of IL-6 correlated with learning and memory performance (R2 = 0.58; p = 0.03), but not motivated behavior, in MRL/lpr mice. Compared to MRL/lpr IL-6 WT, IL-6 KO mice exhibited improved novelty preference on object placement (45.4% vs 60.2%, p < 0.0001) and object recognition (48.9% vs 67.9%, p = 0.002) but equivalent performance in tests for anxiety-like disease and depression-like behavior. IL-6 KO mice displayed decreased cortical expression of aif1 (microglia; p = 0.049) and gfap (astrocytes; p = 0.044). Correspondingly, IL-6 KO mice exhibited decreased density of GFAP + cells compared to IL-6 WT in the entorhinal cortex (89 vs 148cells/mm2, p = 0.037), an area vital to memory. The inflammatory composition of MRL/lpr CSF resembles that of human NPSLE patients. Increased in the CNS, IL-6 is necessary to the development of learning and memory deficits in the MRL/lpr model of NPSLE. Furthermore, the stimulation of entorhinal astrocytosis appears to be a key mechanism by which IL-6 promotes these behavioral deficits.

Predictive Role of Platelet and Inflammation Markers for Severe COVID-19 by Propensity Score Matching.

This study aims to ascertain the predictive value of platelet and inflammation markers in severe cases of COVID-19. A retrospective real-world cohort study was conducted using propensity score matching (PSM). Patients were classified into severe and non-severe COVID-19 groups based on the severity of the disease, and the correlation between severe COVID-19 and laboratory parameters at admission was analyzed. The study included 397 adult patients, comprising 212 (53%) males and 185 (47%) females. Among these, 309 were non-severe and 88 were severe cases. The severe group had a higher median age than the non-severe group (60 vs. 42 years, p < 0.001). Independent risk factors for severe COVID-19 included age, diabetes comorbidity, fever, respiratory symptoms, platelet count, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and the ratio of arterial oxygen partial pressure (PaO2) to the fraction of inspired oxygen (FiO2) (P/F ratio). After one-to-one PSM, adjusted for age, diabetes comorbidities, fever, and respiratory symptoms, significant differences in laboratory parameters at admission were observed. Compared to the non-severe group (n = 71), in the severe group (n = 71), elevated levels of hsCRP (median: 27.1 mg/L vs. 14.6 mg/L, p = 0.005) and IL-6 (median: 16.2 pg/mL vs. 15.3 pg/mL, p = 0.005) were observed, while platelet count (164 ± 36 × 109 vs. 180 ± 50 × 109, p = 0.02) and P/F ratio (median: 351 vs. 397, p = 0.001) were reduced. Elevated levels of hsCRP and IL-6, along with reduced platelet count and P/F ratio at admission, were significantly associated with severe COVID-19 and may serve as predictive indicators.

TRIM27-Induced Protective Autophagy: A Novel Therapeutic Approach for Pneumonia.

Pneumonia is a prevalent respiratory ailment involving complex physiological and pathological mechanisms. The tripartite motif containing 27 (TRIM27) plays a crucial role in regulating inflammation mechanisms. Therefore, the purpose of this study is to further explore the therapeutic potential of TRIM27 in pneumonia, based on its regulatory mechanisms in inflammation and autophagy. This study established a mouse pneumonia animal model through lipopolysaccharide (LPS) administration, designating it as the LPS model group. Subsequently, adenovirus-mediated TRIM27 overexpression was implemented in the animals of the LPS model group, creating the TRIM27 treatment group. After a 7-day treatment period, lung tissues from the mice were collected. Various techniques, including immunohistochemistry, quantitative reverse transcription PCR (RT-qPCR), western blot, enzyme-linked immunosorbent assay (ELISA), and electron microscopy were utilized to analyze the impact of TRIM27 overexpression on inflammatory factors, oxidative stress, autophagy, and inflammatory processes in pulmonary tissues. Finally, an in vitro LPS cell model was established, and the effects of TRIM27 overexpression and autophagy inhibition on inflammatory cytokines and autophagosomes in LPS-induced inflammatory cells were examined through RT-qPCR and immunofluorescence techniques. The research findings demonstrate a significant reduction in the elevated levels of interleukin-6 (IL-6), IL-1β, and Tumor necrosis factor-alpha (TNF-α) induced by LPS with TRIM27 overexpression (p < 0.01). Conversely, the autophagy inhibitor 3-Methyladenine (3-MA) diminished the effects induced by TRIM27 overexpression. Moreover, TRIM27 overexpression enhanced the expression of Microtubule-associated protein 1A/1B light chain 3 (LC3) II/I and Beclin-1 proteins in mice subjected to LPS stimulation (p < 0.01), while reducing the expression of the p62 protein (p < 0.01). The addition of 3-MA, however, decreased Beclin-1 expression and inhibited autophagy (p < 0.01). Additionally, TRIM27 overexpression decreased the expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), cleaved caspase-1, IL-1β, and Gasdermin D N-terminal fragment (GSDMD-N) proteins in LPS-stimulated mice (p < 0.05). TRIM27 overexpression also decreased the levels of malondialdehyde (MDA), Activating Transcription Factor 6 (ATF6), and C/EBP-homologous protein (CHOP), while increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) in mice exposed to LPS (p < 0.01). The induction of TRIM27 overexpression emerges as a potential and effective pneumonia treatment. The underlying mechanism may involve inducing protective autophagy, thereby reducing oxidative stress and cell pyroptosis.

The Correlation Between Interleukin -6 and Dehydroepiandrosterone Sulfate in Patients with Severe COVID-19

Background: Numerous studies have demonstrated that interleukin-6 (IL-6) and serum dehydroepiandrosterone sulfate levels are negatively correlated. Low DHEA-S levels may be associated with severe disease and clinically ailing patients in the context of infectious diseases. Individuals infected with Coronavirus disease who exhibit elevated levels of IL-6 may undergo a cytokine storm, which can result in severe manifestations and a dismal prognosis. Objectives: To examine the relationship between DHEA-S and Il-6 in patients exhibiting severe manifestations of COVID-19. Subjects and Methods: A case-control investigation with 79 patients, ranging in age from 36 to 74 years, who were admitted to the hospital due to severe COVID-19 disease. A control group of 72 ostensibly healthy individuals was also included in the study. Using the ELISA method, the concentrations of IL-6 and DHEA-S in the serum of both groups were determined. The statistical analyses involved the application of the Pearson correlation coefficient and the T-test. None of the authors present any conflicts of interest. Results: With a Pearson correlation coefficient (r) of -0.8349, the study revealed a highly significant negative correlation (P &lt; 0.0001) between the mean IL-6 level (64.369 pg/ml ± 2.6237) and the mean DHEA-S level (1.2728 ng/ml ± 1.7005) in the study group. An exceptionally significant statistical disparity was also identified when IL-6 and DHEA-S levels were compared between the study and control groups. Conclusions: In severely infected COVID-19 patients inverse correlation between the levels of IL-6 and DHEA-S indicates that DHEA-S deficiency may play a role in cytokine storm formation for these patients.

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.

Serum IL-6 predicts risk of kidney transplant failure independently of immunological risk

Interleukin-6 (IL-6) is an important immune mediator and a target for novel antibody therapies. In this study, we aimed to determine whether serum IL-6 levels are associated with immunological risk, allograft rejection and outcomes in kidney transplant (Ktx) patients. We retrospectively analyzed the data of 104 patients who underwent Ktx at our center between 2011 and 2015. The patients were divided into high- and low-risk groups (n = 52 per group) based on panel reactive antibody (PRA) percentage ≥ 35%, the existence of pre-Ktx donor-specific antibodies (DSA), or a previous transplant. IL-6 concentrations were measured before and at 3 months, 12 months, and 3 years after Ktx. Serum IL-6 levels tended to be higher in high-risk patients than in low-risk patients prior to Ktx and at 12 months after Ktx; however, the difference did not reach statistical significance (pre-Ktx, high-risk: 1.995 ± 2.79 pg/ml vs. low-risk: 1.43 ± 1.76 pg/ml, p = 0.051; 12 mo. high-risk: 1.16 ± 1.87 pg/ml vs. low-risk: 0.78 ± 1.13 pg/ml, p = 0.067). IL-6 levels were correlated with the types (no rejection, T cell mediated rejection (TCMR), antibody-mediated rejection (ABMR), or both) and time (<1 year vs. >1 year after Ktx) of rejection, as well as patient and graft survival. Patients with both TCMR and ABMR had significantly higher IL-6 levels at 3 months (14.1 ± 25.2 pg/ml) than patients with ABMR (3.4 ± 4.8 pg/ml, p = 0.017), with TCMR (1.7 ± 1.3 pg/ml, p < 0.001), and without rejection (1.7 ± 1.4 pg/ml, p < 0.001). Three years after Ktx, patients with AMBR had significantly higher IL-6 levels (5.30 ± 7.66 pg/ml) than patients with TCMR (1.81 ± 1.61 pg/ml, p = 0.009) and patients without rejection (1.19 ± 0.95 pg/ml; p = 0.001). Moreover, three years after Ktx IL-6 levels were significantly higher in patients with late rejections (3.5 ± 5.4 pg/ml) than those without rejections (1.2 ± 1.0 pg/ml) (p = 0.006). The risk of death-censored graft failure was significantly increased in patients with elevated IL-6 levels at 12 months (IL-6 level > 1.396 pg/ml, HR 4.61, p = 0.007) and 3 years (IL-6 level > 1.976 pg/ml, HR 6.75, p = 0.003), but elevated IL-6 levels were not associated with a higher risk of death. Overall, our study highlights IL-6 as a risk factor for allograft failure and confirms that IL-6 levels are higher in patients developing ABMR compared to TCMR alone or no rejection.

Hypervolemia in Dialysis Patients Impairs STAT3 Signaling and Upregulates miR-142-3p: Effects on IL-10 and IL-6.

Fluid overload in hemodialysis patients (HD) has been proven to be associated with inflammation. Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) appear to be inadequately counterbalanced by the anti-inflammatory cytokine interleukin-10 (IL-10). We initiated a cross-sectional study enrolling 40 HD patients who were categorized by a bioimpedance measurement in normovolemic (N; 23) and hypervolemic (H; 17) groups to test whether IL-10- and IL-6-related signal transduction pathways (signal transducer of transcript 3: STAT3) and/or a post-transcriptional regulating mechanism (miR-142) are impaired by hypervolemia. IL-10/IL-6 transcript and protein production by PBMCs (peripheral blood mononuclear cells) were determined. Phospho-flow cytometry was used to detect the phosphorylated forms of STAT3 (pY705 and pS727). miR-142-3p/5p levels were detected by qPCR. Hypervolemic patients were older, more frequently had diabetes, and showed higher CRP levels. IL-10 transcripts were elevated in H patients but not IL-10 protein levels. In spite of the elevated mRNA expression of the suppressor of cytokine expression 3 (SOCS3), IL-6 mRNA and protein expression were increased in immune cells of H patients. The percentage of cells staining positive for STAT3 (pY705) were comparable in both groups; in STAT3 (pS727), however, the signal needed for full transactivation was decreased in H patients. miR-142-3p, a proven target of IL-10 and IL-6, was significantly elevated in H patients. Insufficient phosphorylation of STAT3 may impair inflammatory and anti-inflammatory cytokine signaling. How far degradative mechanisms induced by elevated miR-142-3p levels contribute to an inefficient anti-inflammatory IL-10 signaling remains elusive.

TUMOR NECROSIS FACTOR-Α AND INTERLEUKIN-6 IN BLOOD SERUM OF INFANTS AND CHILDREN WITH CONGENITAL HEART DISEASES

The aim of the study was to evaluate the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in infants and children with congenital heart defects (CHD) in comparison with the levels in the control groups. Materials and methods. The volume study included 56 patients, including 35 cyanotic and 21 cyanotic with congenital heart disease, as well as 20 control subjects. We used a specific immunoassay to measure serum ghrelin, TNF-a and IL-6 levels. All patients' cardiac diagnoses were based on clinical examination, laboratory tests, electrocardiography and echocardiography; and none of the patients had pulmonary hypertension. The body mass index (BMI) was calculated as the ratio of body weight (kg) and height squared (m). The study also included 20 healthy infants and children corresponding to age and gender as a control group. Informed consent was obtained from the parents. Results. The results of the analysis indicate a significant increase in IL-6 and TNF-a levels in cyanotic and acyanotic patients with congenital heart defects compared with the control group (P &lt; 0.0001). The findings highlight the importance of cytokines in the pathophysiology of congenital heart defects and their effect on patient growth. It is suggested that elevated levels of IL-6 and TNF-a may stimulate the process of apoptosis, which may play a key role in growth retardation. These data indicate the presence of growth disorders in a significant proportion of patients with congenital heart defects. These results provide additional details about the nature of growth disorders in patients with congenital heart defects and highlight the importance of further research to better understand the molecular and immunological mechanisms associated with this condition. Conclusion. The findings of this study support the hypothesis of the effect of cytokines on growth in congenital heart defects. Elevated levels of IL-6 and TNF-a are likely associated with chronic congestive heart failure and hypoxia. Further research is needed to confirm these results and develop therapeutic strategies for managing growth retardation in children with congenital heart defects.

The Role of Inflammatory Biomarkers in Mediating the Effect of Inflammatory Bowel Disease on nonmalignant Digestive System Diseases: A Multivariable Mendelian Randomized Study.

While observation studies have shown a positive correlation between inflammatory bowel disease (IBD) and the risk of nonmalignant digestive system diseases, a definitive causal relationship has not yet been clearly established. Mendelian randomization (MR) was employed to investigate the potential causal association between genetic susceptibility to IBD and nonmalignant gastrointestinal diseases. Genetic variants were extracted as instrumental variables (IVs) from a genome-wide association study (GWAS) meta-analysis, which included 12,194 cases of Crohn's disease (CD) and 28,072 control cases of European ancestry. The GWAS for ulcerative colitis (UC) included 12,366 UC and 33,609 control cases of European ancestry. All IVs reached genome-wide significance (GWAS p value <5 × 10-8). Summary-level data for acute pancreatitis (AP), irritable bowel syndrome (IBS), gastroesophageal reflux disease, cholelithiasis, and CeD (celiac disease) were obtained from the GWAS meta-analysis and the FinnGen dataset. Summary-level data on relevant inflammatory factors were provided by the International Genetic Consortium. Univariate MR analysis was conducted using inverse variance weighting as the primary method for estimating causal effects. Multivariate MR analyses were also performed to detect possible mediators. Genetic susceptibility to UC was associated with an increased risk of AP (OR = 1.08; 95% CI = 1.03-1.13; p=0.002) and IBS odds ratio (OR] = 1.07; 95% confidence interval (CI] = 1.03-1.11; (p < 0.001). In terms of potential mediators, interleukin 6 (IL-6) had a driving effect on the association between UC and AP. There was no apparent evidence of increased risk with CD. Meanwhile, genetic susceptibility to CD increases the risk of CeD (OR = 1.14; 95% CI = 1.03-1.25; p=0.01). The evidence suggests that UC is associated with an elevated risk of AP and IBS, and IL-6 may be responsible in AP. CD is associated with an increased risk of developing CeD. Implementing a proactive monitoring program for assessing the risk of gastrointestinal diseases in UC patients, particularly those with elevated IL-6 levels, may be of interest. In addition, the presence of AP and IBS may indicate the presence of UC. Preventing CeD is an essential consideration in the therapeutic management of patients with CD.

How is inflammation biology truly associated with depression in patients with stable coronary heart disease?: Insights from the heart and Soul study

Depression is known to be associated with inflammation among patients with established coronary heart disease (CHD), but it is unclear whether this is due to individual depression symptoms or to the broader construct of depression. We addressed this gap by using moderated non-linear factor analysis (MNLFA) to determine the extent that inflammation is associated with latent depression and/or individual symptoms in this patient group. We evaluated 1,024 outpatients with stable CHD from the baseline cross-sectional data of the Heart and Soul Study. Depression was assessed using the 9-item Patient Health Questionnaire, while inflammation was evaluated via C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) levels. MNLFA is based on the concept of model parameter moderation with regard to individual characteristics. Using the MNLFA approach, we simultaneously tested for differences in (1) latent depression, (2) individual depression items, and (3) the factor loading of the item on latent depression as a function of inflammatory markers, with and without covariate adjustment. Higher TNF-α levels were associated with both higher levels of a latent depression factor and greater endorsement of an individual symptom (appetite changes). Increased CRP levels were significantly associated with greater appetite changes, lower concentration difficulty, and greater fatigue. Elevated IL-6 levels were only related to greater fatigue, while increased MCP-1 levels were linked to greater sleep disturbance. After adjusting for covariates, some associations became insignificant. Inflammatory markers were not consistent predictors of factor loadings. This study represents the initial step to discussing how inflammation biology is truly related to depression among patients with established CHD.

Cytokine profiles in dengue fever and dengue hemorrhagic fever: A study from Indonesia

Recent studies have demonstrated that cytokine dysregulation has a critical role in the pathogenesis of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The aim of this study was to investigate the association between tumor necrosis factor (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), and interleukin 17 (IL-17) with infection status, and severity of dengue. A prospective cross-sectional study was conducted at three hospitals in Gianyar regency and Denpasar municipality, Bali, Indonesia, from June to December 2022. Sixty-four dengue infected patients were involved. Patients’ serum was tested for dengue infection using NS1 antigen rapid test, dengue virus immunoglobulin M (IgM) and immunoglobulin G (IgG) test, and reverse transcription polymerase chain reaction (RT-PCR). Cytokine levels (TNF-α, IL-6, IL-10, and IL-17) were measured using enzyme-linked immunosorbent assay (ELISA). Infection status was determined by combining serological and RT-PCR results, categorizing patients into primary and secondary infections. The present study found that DF patients had lower TNF-α, IL-6, and IL-17 but higher IL-10 levels compared to DHF patients (p&lt;0.001). Elevated TNF-α, IL-6, and IL-17 levels were higher in secondary infection, while IL-10 level was higher in primary infection (p&lt;0.001). In conclusion, cytokines play a crucial role in the interplay between cytokine dysregulation and dengue infection dynamics.

Prognostic relevance of the C-X-C motif chemokine ligand 13 and interleukin-8 in predicting the transition from clinically isolated syndrome to multiple sclerosis.

The initial phase of multiple sclerosis (MS), often known as clinically isolated syndrome (CIS), is a critical period for identifying individuals at high risk of progressing to full-blown MS and initiating timely treatment. In this study, we aimed to evaluate the prognostic value of C-X-C motif chemokine ligand 13 (CXCL13) and interleukin-8 (IL-8) as potential markers for CIS patients' conversion to MS. Our study encompassed patients with CIS, those with relapsing-remitting MS (RRMS), and control subjects, with sample analysis conducted on both cerebrospinal fluid (CSF) and serum. Patients were categorized into four groups: CIS-CIS (no MS development within 2 years), CIS-RRMS (conversion to RRMS within 2 years), RRMS (already diagnosed), and a control group (CG) with noninflammatory central nervous system disorders. Results showed significantly elevated levels of CXCL13 in CSF across all patient groups compared with the CG (p < 0.0001, Kruskal-Wallis test). Although CXCL13 concentrations were slightly higher in the CIS-RRMS group, statistical significance was not reached. Similarly, significantly higher levels of IL-8 were detected in CSF samples from all patient groups compared with the CG (p < 0.0001, Kruskal-Wallis test). Receiver operating characteristic analysis in the CIS-RRMS group identified both CXCL13 (area under receiver operating characteristic curve = .959) and IL-8 (area under receiver operating characteristic curve = .939) in CSF as significant predictors of CIS to RRMS conversion. In conclusion, our study suggests a trend towards elevated CSF IL-8 and CSF CXCL13 levels in CIS patients progressing to RRMS. These findings emphasize the importance of identifying prognostic markers to guide appropriate treatment strategies for individuals in the early stages of MS.