Eotaxin Levels Research Articles

Oral administration of Limosilactobacillus reuteri VHProbi® M07 alleviates ovalbumin-induced allergic asthma in mice.

Asthma is characterized by chronic airway inflammation, persistent cough, wheezing, and dyspnea. This study aimed to evaluate the efficacy of Limosilactobacillus reuteri VHProbi® M07 (M07) administration in alleviate the asthma severity in a mice model. In vitro studies confirmed that M07 can survive and proliferate within the gastrointestinal tract. BALB/c mice were administered M07 both before and after ovalbumin (OVA) challenge. Serum levels of OVA-specific immunoglobulin (Ig) E and IgG1, inflammatory cells and cytokines in bronchoalveolar lavage fluid were assessed, along with histopathological examination of lung tissue. Compared to the placebo (PLA) group, mice treated with M07 exhibited significantly lower levels of OVA-specific IgE and IgG1 (P < 0.01). The counts of eosinophils and neutrophils were also significantly reduced in both the pretreated (PRE) group and post-treated (POS) group compared with the PLA group (P < 0.01). Histological analysis of lung tissues verified the protective effects of M07 against inflammation, demonstrating reduced infiltration of inflammatory cells. Additionally, mice in the PRE and POS groups showed significantly increased levels of IL-10 (P < 0.01), and significantly decreased levels of IL-5, IL-13, MCP-1, eotaxin, and tumor necrosis factor-α (P < 0.01). Oral administration of M07 mitigated key features of inflammatory responses in the OVA-induced mice asthma model. These findings suggest that M07 holds therapeutic potential for the treatment of allergic asthma.

Inflammatory proteins and vestibular neuronitis: A Mendelian randomization study.

Previous studies have highlighted the correlation between inflammatory responses and vestibular neuritis (VN). The aim of Mendelian randomization was to assess the causal associations between 91 inflammatory proteins and vestibular neuritis comprehensively. By leveraging publicly accessible genetic datasets, we probed whether 91 inflammatory proteins serve as upstream determinants of vestibular neuritis. We conducted a comprehensive sensitivity analysis to assess the robustness, heterogeneity, and polygenicity of our findings. Three inflammatory proteins were found to exert a significant causal effect on the VN: eotaxin levels are associated with a reduced risk of VN (inverse variance weighting [IVW]: odds ratio [OR] = 0.7113, 95% confidence intervals [CI] = 0.5199-0.9731, P = .0331). Similarly, the measurement of monocyte chemotactic protein-2 is linked to a decreased risk of VN (IVW: OR = 0.8535, 95% CI = 0.7328-0.9942, P = .0418). Conversely, an increase in the level of the T-cell surface glycoprotein CD5 is correlated with an increased risk of VN (IVW: OR = 1.3969, 95% CI = 1.0095-1.9331, P = .0437). This study suggested that eotaxin, monocyte chemotactic protein-2, and the T-cell surface glycoprotein CD5 may play crucial roles in the pathogenesis of VN. The potential use of these inflammatory proteins for diagnosing VN or as therapeutic targets has significant clinical implications.

Altered eotaxin-1 and interleukin-34 levels in obsessive-compulsive disorder: a case-control observational study in Bangladesh.

Obsessive-compulsive disorder (OCD) is a prevalent mental health condition that impacts daily life. It is thought to be associated with genetic, biological, and structural brain changes, serotonergic abnormalities, altered neuromodulation, and environmental factors. Limited observational studies have examined cytokines in Bangladeshi patients with OCD. This study aimed to assess the levels of eotaxin-1 and interleukin (IL)-34 in individuals with this disorder. This case-control observational study included 58 patients with OCD and 30 healthy controls (HCs) matched for age, sex, and body mass index. The severity of OCD was assessed using the Yale-Brown obsessive-compulsive scale (Y-BOCS). Psychiatrists evaluated participants according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Serum levels of eotaxin-1 and IL-34 were measured using enzyme-linked immunosorbent assay kits. Patients with OCD exhibited significantly higher serum eotaxin-1 levels (121.13±7.84 pg/mL) than HCs (85.52±9.42 pg/mL). Conversely, IL-34 levels were considerably lower in patients than in HCs (119.02±14.53 pg/mL vs. 179.96±27.88 pg/mL). The Cohen d values for eotaxin-1 and IL-34 were 0.55 and -0.48, respectively. Among patients with OCD, a significant positive correlation was found between serum eotaxin-1 level and Y-BOCS score, along with a negative correlation between serum eotaxin-1 and IL-34 levels. The findings suggest that altered eotaxin-1 and IL-34 levels may be associated with OCD. These chemokines and cytokines could serve as primary tools for assessing the risk of OCD, warranting further clinical investigation. This could potentially support more extensive research and the development of diagnostic and therapeutic strategies targeting these pathways.

Serum cytokines as a biomarker for immune checkpoint inhibitor toxicity in patients with pleural mesothelioma.

Pleural mesothelioma (PM) is a rare cancer with a dismal prognosis. Dual immune checkpoint inhibitors have improved overall survival, but the rate of immune-related adverse events (irAEs) is high. Serum cytokines reflect systemic immune reactions and may serve as biomarkers for irAEs. Patients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Serum cytokine levels were measured by Bio-Plex Pro Human Cytokine Screening 48-Plex Panel Assay. Correlations between cytokine levels and irAEs were analyzed by generalized linear mixed models to identify potential diagnostic and predictive biomarkers. Higher levels of MIG, eotaxin, MIP-1α, IP-10, TNF-α, MIP-1β, IL-4, MIF, IL-16, IL-2RA, SCGF.β and PDFG-BB at baseline are associated with increased risk of developing one or more irAEs. In particular, higher baseline levels of MIG are positively associated with thyroiditis and hypophysitis, and elevated levels of IP-10 and MIG to dermatitis. During the course of treatment, higher levels of MIG, eotaxin, MIF, TNF-α, MIP-1β, IL-4 and IL-16 are associated with an ongoing irAE. We found both predictive and diagnostic value of MIF with fatigue and of eotaxin with both colitis and pneumonitis. Higher levels of CTACK is associated with a lower risk of developing hepatitis, both before and after treatment. Elevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES.

A Two-Year cohort study examining the impact of cytokines and chemokines on cognitive and psychiatric outcomes in Long-COVID-19 patients.

This study investigates the relationship between clinical, sociodemographic, and neuropsychological symptoms and serum cytokine concentrations with long-term cognitive and psychiatric outcomes in long-COVID-19 patients. We reassessed 108 adults who survived moderate to severe COVID-19 at two intervals post-discharge (T1, mean 6.9 months; T2, mean 23.5 months). Baseline sociodemographic and clinical data were collected from hospital records, while cognitive and mental health assessments included psychometric tests such as the Hospital Anxiety and Depression Scale (HADS) and Immediate and Delayed Recall Tests from the CERAD Battery. Serum cytokine levels were measured at T1. Generalized Additive Models (GAMs), Elastic Net Regression (NET), and Psychological Network Analysis (PNA) were used to analyze the data. The GAM analysis revealed significant associations between acute COVID-19 severity and Epworth Sleepiness Score with persistent anxiety symptoms at T2. For depression, both WHO severity class and Eotaxin levels were significant predictors. The Anti-inflammatory Index showed a marginally significant relationship with immediate recall, while age was marginally associated with delayed recall performance. In NET, only anxiety was significantly associated with Epworth Sleepiness Score, WHO severity class, and Proinflammatory Index. PNA did not reveal direct connections between cytokines and neuropsychological outcomes in the graphical model. However, centrality measures indicated that the Proinflammatory Index and VEGF were more central within the network, suggesting they might be important components of the overall system. This study provides insights into the complex role of cytokines and inflammation in long-COVID-19 outcomes, potentially aiding in the identification of biomarkers for diagnosis and prognosis.

Chemokine associations with blood cerebrospinal fluid barrier permeability and delirium

Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, directly impairing brain function. It is not known whether these molecules reach higher brain levels when the blood cerebrospinal fluid barrier (BCSFB) is impaired. Here, in human hip-fracture patients, we tested the influence of BCSFB integrity on CSF levels of chemokines and assessed their association with delirium. CSF levels of IP-10, eotaxin, eotaxin 3 and TARC showed weak to moderate correlations with BCSFB permeability, as measured by the Qalbumin ratio, while MCP1, IL-8, MIP1α and MIP1β showed no significant correlation. Chemokines were not associated with delirium in univariate analysis or when stratified on dementia status, but exploratory analyses showed that elevated Eotaxin (CCL11) and MIP1α (CCL3) were associated with prevalent delirium. Modelling acute systemic inflammation, we used bacterial LPS (250 μg/kg) or sterile laparotomy surgery in mice to demonstrate de novo synthesis of chemokines at the choroid plexus (CP) and microvasculature. Gene expression data showed CP-enriched expression of Il1b, Tnfa, Cxcl1 and Ccl3 in both models and immunohistochemistry showed cytokine and chemokine synthesis in CP stromal (IL-1β, CCL2/MCP1) or epithelial cells (CXCL10/IP-10) cells and at the microvasculature. Larger studies are required to confirm these human findings on chemokine associations with BCSFB permeability and prevalent delirium. Preclinical studies are warranted to determine whether chemokines might play a role in the pathophysiology of delirium.

Relation of 91 Circulating Inflammatory Proteins to Nonalcoholic Fatty Liver Disease: A Two‐Sample Mendelian Randomisation Study

ABSTRACTIncreasingly, emerging research evidence has demonstrated that nonalcoholic fatty liver disease (NAFLD) is a disease closely associated with systemic inflammation. However, the specific upstream inflammatory factors engaged in the pathogenesis of NAFLD remain unclear. Our study aimed to identify the inflammatory regulators causally associated with NAFLD pathogenesis through Mendelian randomisation. A two‐sample Mendelian randomisation method was applied to analyse the causal association between 91 circulating inflammatory proteins and NAFLD. Data on circulating inflammatory proteins were derived from samples of European ancestry (14,824 samples) and NAFLD data were obtained from the FinnGen consortium (2025 cases and 284,826 controls). Instrumental variables were selected from the genetic variance and F‐statistics were calculated to avoid bias. We adopted the random‐effects inverse variance weighting (IVW) method as our primary analytical approach. Supplementary analyses were also implemented, including weighted median, MR‐Egger and weighted mode. Moreover, we conducted pleiotropy and heterogeneity analyses to validate the accuracy of the findings. The application of Mendelian randomisation analysis identified four inflammatory factors that might be causally associated with NAFLD at the genetic level. Elevated levels of eotaxin (or = 1.27, 95% CI: 1.05–1.53, p = 0.014), osteoprotegerin (OPG) (or = 1.29, 1.03–1.60, p = 0.023) and TNFRSF9 (or = 1.32, 95% CI: 1.06–1.64, p = 0.014) may be causally related to an increasing risk of NAFLD. Conversely, heightened leukaemia inhibitory factor (LIF) levels (or = 0.63, 0.44–0.92, p = 0.016) were linked to a lower risk of NAFLD onset. There was no causal relationship between levels of other circulating inflammatory proteins and NAFLD. Our analysis uncovered four upstream inflammatory factors genetically associated with the pathogenesis of NAFLD. These results highlight the potential involvement of inflammation in NAFLD, which provides partial insights for further research in this field in the future.

Paraprobiotic Levilactobacillus brevis KU15151 exhibits antioxidative and anti-inflammatory activities in LPS-induced A549 cells

Levilactobacillus brevis KU15151, isolated from kimchi, has been reported in previous studies to possess probiotic properties. Here, we sought to explore the potential of heat-killed L. brevis KU15151 in improving respiratory health by identifying its antioxidant and anti-inflammatory effects in LPS-induced A549 cells. Inactivated L. brevis KU15151 exhibited strong DPPH and ABTS radical-scavenging abilities (48.78 ± 3.95 % and 69.08 ± 1.09 %) and effectively reduced the production of reactive oxygen species (25.32 %). In addition, it was found to have anti-inflammatory effects by inhibiting phosphorylation of ERK 1/2 (0.556), JNK (0.476), p38 MAPK (0.580), p65 (0.579), and IκB-α (1.170), which are involved in MAPK and NF-κB signaling. It also suppressed the mRNA expression of pro-inflammatory cytokines (0.173–0.617), which are important factors in respiratory diseases. IL-6 (19.47 %) and eotaxin (50.19 %) levels were reduced as measured by ELISA. Therefore, heat-killed L. brevis KU15151 is expected to improve respiratory health.

Leptin augments IL-13-induced airway eotaxins and submucosal eosinophilia in obesity-associated asthma

BackgroundAirway tissue eosinophilia can be an observed feature of obesity associated T2 asthma, but the processes mediating this inflammation are unknown. ObjectiveWe investigated a process whereby leptin, an adipokine elevated in obesity, potentiates pulmonary eosinophilia and eotaxin production by airway fibroblasts in T2 asthma. MethodsWe assessed associations between body mass index and airway eosinophilia, leptin and eotaxin production in 78 asthma participants, 36 of which exhibited obesity. Cultured human airway fibroblasts and mouse models of chronic allergic airway disease were used to evaluate leptin’s effect on eotaxin production and lung eosinophilia. The role of interleukin-13 receptor alpha 2 (IL-13Rα2) in mediating these processes was examined using specific neutralizing antibodies in vitro. ResultsIn T2 asthma participants with obesity, we observed that airway tissue eosinophilia did not associate with traditional T2 inflammation metrics such as peripheral and/or bronchoalveolar lavage fluid (BALF) eosinophil counts or with fractional concentration of exhaled nitric oxide (FeNO). Alternatively, we observed elevated BALF leptin and eotaxin-1 levels. In airway fibroblasts from asthma participants, leptin augmented IL-13-induced eotaxin-1 and -3 production and IL13RA2 expression. In mice, elevated leptin promoted airway IL-13Rα2 and eotaxin production by lung fibroblasts and lung tissue eosinophilia following chronic house dust mite allergen exposure. Inhibition of IL-13Rα2 reduced combined leptin and IL-13-stimulated eotaxin secretion by human airway fibroblasts. ConclusionWe identified a potential association explaining airway tissue eosinophil retention in obesity-associated T2 asthma through leptin-mediated enhancement of IL-13-induced eosinophil chemokine production by airway fibroblasts, a process requiring IL-13Rα2.

Skin Surface Lipid-RNA Profile Obtained from Patients with Severe Asthma After Benralizumab Treatment.

Examining human coding and non-coding RNAs present in skin surface lipids (SSL-RNAs) offers a promising approach to understanding the physiological state of the skin. Benralizumab treatment can reduce exacerbations and improve symptom control and quality of life in patients with severe eosinophilic asthma. Although this treatment effectively depletes peripheral blood eosinophils, the impact of benralizumab on SSL-RNA remains completely unknown. To investigate the effects of benralizumab treatment on SSL-RNA profiles in patients with severe asthma. Skin samples were non-invasively collected from patients before and after one year of benralizumab treatment. Sixteen patients were enrolled, but the SSL-RNA analysis was only feasible for five patients due to collection challenges, mainly in female participants. Following benralizumab treatment, asthma symptoms, exacerbation rates, and lung function parameters improved. Peripheral blood eosinophils were completely depleted and serum eotaxin-1 levels increased. SSL-RNA analysis revealed differential expression of 134 genes, with significant downregulation of immune-related pathways and genes associated with neutrophilic inflammation. These findings suggest a suppression of both type 2 and non-type 2 inflammation in response to benralizumab treatment, with potential implications for asthma management. However, the limitations of the study include a small sample size and challenges in sebum collection, particularly among female participants. Although the noninvasive nature of this sampling method makes it attractive for both research and clinical applications, additional studies are needed to fully investigate the potential of SSL-RNA analysis as a noninvasive biomarker to assess treatment response in asthma.

Dupilumab Use in Patients With Hypereosinophilic Syndromes: A Multicenter Case Series and Review of the Literature

BackgroundHypereosinophilic syndromes (HES) are defined as hypereosinophilia with eosinophil-related clinical manifestations, some of which overlap in presentation with asthma, atopic dermatitis, eosinophilic esophagitis, and/or chronic rhinosinusitis with nasal polyps (CRSwNP). Dupilumab is approved to treat these conditions but can induce a transient rise in the absolute eosinophil count (AEC) and rare eosinophil-related complications. ObjectiveTo determine whether eosinophil-related complications of dupilumab are increased in HES. MethodsRetrospective chart review of patients with HES treated with dupilumab enrolled on an IRB-approved research protocol at the National Institutes of Health (NCT00001406) or receiving care at Walter Reed National Military Medical Center. Clinical response and treatment-emergent adverse events were recorded. Serum mediators were assessed in a subset of patients before and after dupilumab using stored samples. ResultsAmong the 28 patients (15 male, 13 female; median age 41.5), the most common prescribing indication for dupilumab was CRSwNP (n=11). Twenty-three patients (82%) showed significant clinical improvement on dupilumab. Hypereosinophilia (AEC >1.5x109/L) recurred or worsened in 9/20 patients on dupilumab monotherapy. Moreover, 4/20 (20%) patients developed an eosinophil-related complication with dupilumab discontinuation and/or addition of eosinophil-lowering therapy. None of the 8 patients who received dupilumab while in hematologic remission on an eosinophil-lowering biologic developed hypereosinophilia or an eosinophil-related complication. Serum IgE and eotaxin levels decreased on dupilumab therapy. ConclusionThese data suggest that dupilumab is effective in treating residual symptoms in HES patients but that the incidence of eosinophil-related complications is increased. Concomitant eosinophil-lowering therapy may reduce the risk of eosinophil-related complications during dupilumab therapy in patients with HES.

Plasma exchange with albumin replacement for Alzheimer's disease treatment induced changes in serum and cerebrospinal fluid inflammatory mediator levels.

There is extensive literature indicating that inflammatory pathways are affected in Alzheimer's disease (AD). We examined whether plasma exchange with albumin replacement (PE-Alb) can impact the inflammatory status of AD patients and alter the relationship between inflammatory mediators and cognitive measures. Serum and cerebrospinal fluid (CSF) samples from 142 AD patients participating in the AMBAR trial (14-month schedule of PE-Alb treatment vs. placebo [sham PE-Alb]) were analyzed for changes from baseline for 19 inflammatory mediators (6 inflammatory cytokines, 9 chemokines, and 4 vascular injury indicators) at representative time points across the AMBAR study (lasting effects) as well as in pre- versus post-PE-Alb procedure (acute effects). Association between mediator changes and clinical outcomes reported in the AMBAR study (cognitive, functional, behavioral function, and global change tests) was assessed. PE-Alb significantly reduced IFN-γ, eotaxin, MIP-1α and ICAM-1 levels in serum, and eotaxin-3 and MIP-1β levels in CSF, at various time points during treatment (p < 0.05; false discovery rate-corrected). Vascular injury indicators were the mediators mostly affected by post- versus pre-PE-Alb level reduction. Increased serum MIP-1α levels were associated with worsening in ADAS-Cog, CDR-sb, and ADCS-CGIC scores in the placebo group, but not in the PE-Alb-treated group. Peripheral intervention could affect AD by reducing inflammatory mediators in both peripheral and central compartments. Changes in MIP-1α due to PE-Alb were associated with changes in clinical outcomes.

Genetic insights into the causal linkage between systemic inflammatory regulators and frailty

ObjectivesPrevious studies have suggested the associations between systemic inflammation and the risk of frailty, but causal relationships between them remain not well established. We conducted a bi-directional Mendelian randomization (MR) analysis to investigate the causal links between systemic inflammatory regulators and frailty. MethodsGenetic variants associated with systemic inflammatory regulators were obtained from a comprehensive genetic study on 41 circulating cytokines, such as interleukin-4 (IL-4), eotaxin, and macrophage inflammatory protein-1β (MIP1β). We integrated summary-level data on frailty from two independent genetic studies on frailty index (FI) and Fried frailty score (FFS). The inverse-variance weighted method was used to assess the causal estimate. Sensitivity and heterogeneity analysis was performed to evaluate the stability of the estimates. The false discovery rate (FDR) method was used for P value adjustment of multiple comparisons. ResultsGenetically elevated levels of MIP1β and decreased levels of eotaxin were suggestively associated with increased FI (MIP1β: β = 0.016, Praw = 0.006, PFDR = 0.083; eotaxin: β = -0.030, Praw = 0.007, PFDR = 0.083) and FFS (MIP1β: β = 0.008, Praw = 0.027, PFDR = 0.247; eotaxin: β = -0.015, Praw = 0.014, PFDR = 0.247). In contrast, genetically predicted FI was suggestively associated with decreased levels of IL-4 (β = -0.395, Praw = 0.040, PFDR = 0.638) and platelet-derived growth factor BB (PDGF-BB, β = -0.385, Praw = 0.047, PFDR = 0.638) and increased levels of stem cell factor (SCF, β = 0.527, Praw = 0.005, PFDR = 0.204). Similar results were obtained from different sensitivity analysis. ConclusionsThe present study demonstrates that increased MIP-1β levels and decreased eotaxin levels might lead to a higher risk of frailty, whereas frailty might reduce the levels of IL-4 and PDGF-BB and increase the levels of SCF.

The role of circulating cytokines in heart failure: a bidirectional, two-sample Mendelian randomization study.

Cytokines play a pivotal role in the progression of heart failure (HF) by modulating inflammatory responses, promoting vasoconstriction, and facilitating endothelial injury. However, it is now difficult to distinguish the causal relationship between HF and cytokines in observational studies. Mendelian randomization (MR) analyses of cytokines probably could enhance our comprehension to the underlying biological processes of HF. This study was to explore the correlation between 41 cytokines with HF at the genetic level by MR analysis. We selected a HF dataset from the Heart Failure Molecular Epidemiology for Therapeutic Targets (HERMES) 2018 and a cytokine dataset from a meta-analysis of cytokine levels in Finns. Two-sample, bidirectional MR analyses were performed using Inverse Variance Weighted (IVW), Weighted Median and MR- egger, and the results were tested for heterogeneity and pleiotropy, followed by sensitivity analysis. Genetic prediction of high levels of circulating Macrophage inflammatory pro-tein-1β(MIP-1β) (P = 0.0389), Interferon gamma induced protein 10(IP-10) (P = 0.0029), and Regu-lated on activation, normal T cell expressed and secreted(RANTES) (P = 0.0120) expression was associated with an elevated risk of HF. HF was associated with the increased levels of circulating Interleukin-2 receptor, alpha subunit(IL-2ra) (P = 0.0296), Beta nerve growth fac-tor(β-NGF) (P = 0.0446), Interleukin-17(IL-17) (P = 0.0360), Basic fibroblast growth factor(FGF-basic) (P = 0.0220), Platelet derived growth factor BB(PDGF-BB) (P = 0.0466), and Interferon-gamma(IFN-γ) (P = 0.0222); and with decreased levels of Eotaxin (P = 0.0133). The heterogeneity and pleiotropy of the cytokines were acceptable, except for minor heterogeneity of FGF-basic and IL-17. These findings provide compelling evidence for a genetically predictive relationship between cytokines and HF, emphasizing a great potential of targeted modulation of cytokines in slowing the progression of HF. This study draws further conclusions at the genetic level, providing a basis for future large-scale clinical trials.

Predicting Vasospasm and Early Mortality in Severe Traumatic Brain Injury: A Model Using Serum Cytokines, Neuronal Proteins, and Clinical Data.

Prediction of patient outcomes after severe traumatic brain injury (sTBI) is limited with current clinical tools. This study aimed to improve such prognostication by combining clinical data and serum inflammatory and neuronal proteins in patients with sTBI to develop predictive models for post-traumatic vasospasm (PTV) and mortality. Fifty-three adult civilian patients were prospectively enrolled in the sTBI arm of the Surgical Critical Care Initiative (SC2i). Clinical, serum inflammatory, and neuronal protein data were combined using the parsimonious machine learning methods of least absolute shrinkage and selection operator (LASSO) and classification and regression trees (CART) to construct parsimonious models for predicting development of PTV and mortality. Thirty-six (67.9%) patients developed vasospasm and 10 (18.9%) died. The mean age was 39.2 years; 22.6% were women. CART identified lower IL9, lower presentation pulse rate, and higher eotaxin as predictors of vasospasm development (full data area under curve (AUC) = 0.89, mean cross-validated AUC = 0.47). LASSO identified higher Rotterdam computed tomography score and lower age as risk factors for vasospasm development (full data AUC 0.94, sensitivity 0.86, and specificity 0.94; cross-validation AUC 0.87, sensitivity 0.79, and specificity 0.93). CART identified high levels of eotaxin as most predictive of mortality (AUC 0.74, cross-validation AUC 0.57). LASSO identified higher serum IL6, lower IL12, and higher glucose as predictive of mortality (full data AUC 0.9, sensitivity 1.0, and specificity 0.72; cross-validation AUC 0.8, sensitivity 0.85, and specificity 0.79). Inflammatory cytokine levels after sTBI may have predictive value that exceeds conventional clinical variables for certain outcomes. IL-9, pulse rate, and eotaxin as well as Rotterdam score and age predict development of PTV. Eotaxin, IL-6, IL-12, and glucose were predictive of mortality. These results warrant validation in a prospective cohort.

Profiling neuroinflammatory markers and response to nusinersen in paediatric spinal muscular atrophy.

Neuroinflammation is an emerging clinical feature in spinal muscular atrophy (SMA). Characterizing neuroinflammatory cytokines in cerebrospinal fluid (CSF) in SMA and their response to nusinersen is important for identifying new biomarkers and understanding the pathophysiology of SMA. We measured twenty-seven neuroinflammatory markers in CSF from twenty SMA children at different time points, and correlated the findings with motor function improvement. At baseline, MCP-1, IL-7 and IL-8 were significantly increased in SMA1 patients compared to SMA2, and were significantly correlated with disease severity. After six months of nusinersen treatment, CSF levels of eotaxin and MIP-1β were markedly reduced, while IL-2, IL-4 and VEGF-A were increased. The decreases in eotaxin and MIP-1β were associated with changes in motor scores in SMA1. We also detected a transient increase in MCP-1, MDC, MIP-1α, IL-12/IL-23p40 and IL-8 after the first or second injection of nusinersen, followed by a steady return to baseline levels within six months. Our study provides a detailed profile of neuroinflammatory markers in SMA CSF. Our data confirms the potential of MCP-1, eotaxin and MIP-1β as new neuroinflammatory biomarkers in SMA1 and indicates the presence of a subtle inflammatory response to nusinersen during the early phase of treatment.

Differences of in vitro immune responses between patent and pre-patent Litomosoides sigmodontis-infected mice are independent of the filarial antigenic stimulus used.

Lymphatic filariasis and onchocerciasis are neglected tropical diseases and cause significant public health problems in endemic countries, especially in sub-Saharan Africa. Since the human parasites are not viable in immune-competent mice, animal models have been developed, among them Litomosoides sigmodontis which permits a complete life cycle in BALB/c mice, including the development of patent infections with circulating microfilariae (Mf, the worm's offspring). To investigate the immunomodulatory properties of helminths in vitro, antigenic extracts can be prepared from different life cycle stages of the L. sigmodontis model, including adult worms, but the methods to prepare these antigens differ between research groups. This study analyzed whether different centrifugation methods during the preparation of an antigenic extract, the gender of used worms, or the different fractions (soluble or pellet) altered filarial-specific CD4+ Tcell responses. These cells were isolated from pre-patent or patent/chronic infected mice, hence those without and those with Mf, respectively. Ex vivo immune responses were compared at these two different time points of the infection as well as the parasitic parameters. Worm burden and cell infiltration were elevated in the thoracic cavity (TC) and draining mediastinal lymph nodes at the pre-patent stage. Within the TC, eosinophils were significantly up-regulated at the earlier time point of infection which was further reflected by the eosinophil-related eotaxin-1 levels. Regarding the production of cytokines by re-stimulated CD4+ T cells in the presence of different antigen preparations, cytokine levels were comparable for all used extracts. Our data show that immune responses differ between pre-patent and patent filarial infection, but not in response to the different antigenic extracts themselves.

Effect of inflammatory cytokines and plasma metabolome on OSA: a bidirectional two- sample Mendelian randomization study and mediation analysis.

Obstructive sleep apnea (OSA) is a common sleep disorder. Inflammatory factors and plasma metabolites are important in assessing its progression. However, the causal relationship between them and OSA remains unclear, hampering early clinical diagnosis and treatment decisions. We conducted a large-scale study using data from the FinnGen database, with 43,901 cases and 366,484 controls for our discovery MR analysis. We employed 91 plasma proteins from 11 cohorts (totaling 14,824 participants of European descent) as instrumental variables (IVs). Additionally, we conducted a GWAS involving 13,818 cases and 463,035 controls to replicate the MR analysis. We primarily used the IVW method, supplemented by MR Egger, weighted median, simple mode, and weighted mode methods. Meta-analysis was used to synthesize MR findings, followed by tests for heterogeneity, pleiotropy, and sensitivity analysis (LOO). Reverse MR analysis was also performed to explore causal relationships. The meta-analysis showed a correlation between elevated Eotaxin levels and an increased risk of OSA (OR=1.050, 95% CI: 1.008-1.096; p < 0.05). Furthermore, we found that the increased risk of OSA could be attributed to reduced levels of X-11849 and X-24978 (decreases of 7.1% and 8.4%, respectively). Sensitivity analysis results supported the reliability of these findings. In this study, we uncovered a novel biomarker and identified two previously unknown metabolites strongly linked to OSA. These findings underscore the potential significance of inflammatory factors and metabolites in the genetic underpinnings of OSA development and prognosis.

Proton pump inhibitors modulate esophageal epithelial barrier function and crosstalk with eosinophils.

Eosinophilic esophagitis (EoE) is a chronic allergic disease characterized by esophageal dysfunction, type-2 inflammation, and esophageal eosinophilic infiltrate. While proton pump inhibitor (PPI) therapy is commonly used for EoE management, the underlying mechanism of action remains unclear. Air-liquid interface culture of esophageal epithelial cells was employed to investigate the impact of the PPI omeprazole on barrier integrity in IL-13-treated cultures. Epithelial chemokine secretion was assessed following stimulation with IL-13 and omeprazole, and the migration of eosinophils from healthy human donors was evaluated using 3 μm pore-sized transwells. A co-culture system of epithelial cells and eosinophils was employed to study chemokine secretion and eosinophil adhesion and activation markers. Omeprazole treatment in the IL-13-treated air-liquid interface (ALI) model resulted in 186 differentially expressed genes and restored barrier integrity compared to ALI treated with IL-13 alone. Omeprazole treatment reduced STAT6 phosphorylation, downregulated calpain 14, and upregulated desmoglein-1 in the IL-13-treated air-liquid interface samples. IL-13-induced upregulation of Eotaxin-3, CXCL10, and periostin, but this was downregulated by omeprazole. Further, the expression of CD11b, CD18, and CD69 was lower on eosinophils from omeprazole-treated epithelial-eosinophil co-cultures, which also had lower levels of eotaxin-3, CXCL10, CCL2, and CCL4. Omeprazole reduced the effects of IL-13 in both the epithelial air-liquid interface model and eosinophil-epithelial co-cultures, reducing barrier dysfunction, chemokine expression, and upregulation of eosinophil adhesion markers.

Immunologic analysis of CSF in patients with de novo diagnosed RRMS. The role of chemokines in the early phase of the disease

Objectives: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by demyelination and neurodegeneration. Chemokines regulate leukocyte migration and inflammation in MS. In the present study, we evaluated selected chemokine levels in the cerebrospinal fluid of patients with multiple sclerosis diagnosed de novo compared to healthy controls.Methods: We measured EOTAXIN, IP-10, MCP-1, MIP-1a, MIP-1b and RANTES in the cerebrospinal fluid of 118 patients with de novo RRMS and 112 controls, analyzing correlations with time from symptom onset to diagnosis and changes in MRI.Results: Higher levels of EOTAXIN, IP-10, MIP-1B and RANTES, and lower MCP-1 were observed in MS patients compared to controls. MIP-1A did not show statistical significance. EOTAXIN and IP-10 concentrations increased with time. RANTES concentration correlated positively with T2 changes in MRI of the cervical spine, and EOTAXIN concentration correlated negatively with gadolinium (Gd+) changes in the cervical spine. There was no correlation with changes in the thoracic spine or brain.Conclusions: Chemokines play a significant role in the early phase of MS by influencing inflammatory activity. They may represent potential therapeutic targets for the treatment of this disease.