Eotaxin Levels Research Articles

Systemic Immune Profile Predicts the Development of Infections in Patients with Spinal Cord Injuries.

Patients with spinal cord injury (SCI) frequently develop infections that may affect quality of life, be life-threatening, and impair their neurological recovery in the acute and subacute injury phases. Therefore, identifying patients with SCI at risk for developing infections in this stage is of utmost importance. We determined the systemic levels of immune cell populations, cytokines, chemokines, and growth factors in 81 patients with traumatic SCI at 4 weeks after injury and compared them with those of 26 age-matched healthy control subjects. Patients who developed infections between 4 and 16 weeks after injury exhibited higher numbers of neutrophils and eosinophils, as well as lower numbers of lymphocytes and eotaxin-1 (CCL11) levels. Accordingly, lasso logistic regression showed that incomplete lesions (American Spinal Injury Association Impairment Scale [AIS] C and D grades), the levels of eotaxin-1, and the number of lymphocytes, basophils, and monocytes are predictive of lower odds for infections. On the other hand, the number of neutrophils and eosinophils as well as, in a lesser extent, the levels of IP-10 (CXCL10), MCP-1 (CCL2), BDNF [brain-derived neurotrophic factor], and vascular endothelial growth factor [VEGF]-A, are predictors of increased susceptibility for developing infections. Overall, our results point to systemic immune disbalance after SCI as predictors of infection in a period when infections may greatly interfere with neurological and functional recovery and suggest new pathways and players to further explore novel therapeutic strategies.

Serum cytokine changes induced by direct hemoperfusion with polymyxin B-immobilized fiber in patients with acute respiratory failure.

Polymyxin B-immobilized Fiber therapy (PMX-DHP) may improve the prognosis of patients with rapidly progressive interstitial lung diseases (ILDs). However, the mechanisms by which PMX-DHP ameliorates oxygenation are unclear. The present study aimed to clarify the changes in serum cytokine concentrations during PMX-DHP with steroid pulse therapy. Patients with acute respiratory failure (ARF) and rapidly progressive ILDs, acute exacerbation of idiopathic pulmonary fibrosis (IPF), or acute respiratory distress syndrome (ARDS), and treated with PMX-DHP were assessed, including patients with IPF. The serum concentrations of 38 cytokines were compared between the ARF and IPF groups before treatment. In the ARF group, cytokine levels were compared before, immediately after PMX-DHP, and the day after termination of steroid pulse therapy. Fourteen ARF and eight IPF patients were enrolled. A comparison of the cytokine levels before treatment initiation revealed that EGF, GRO, IL-10, MDC, IL-12p70, IL-15, sCD40L, IL-7, IP-10, MCP-1, and MIP-1β were significantly different between the two groups. In the ARF group treated with PMX-DHP, the concentrations of MDC, IP-10, and TNF-α continuously decreased during treatment (P<0.01). Further, the cytokine levels of GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 decreased after the entire treatment period, with no change observed during the steroid-only period (P<0.01, except GRO and MCP-1). Although PMX-DHP significantly reduced eotaxin and GM-CSF serum levels (P<0.01 and P<0.05), these levels did not change after treatment. PMX-DHP combined with steroid pulse therapy might reduce GRO, IL-10, IL-1Ra, IL-5, IL-6, and MCP-1 levels in ARF, contributing to better oxygenation in the disorder.

Type-2 Cytokines Promote the Secretion of the Eosinophil-Attractant CCL26 by Intestinal Epithelial Cells in Food-Sensitized Patients.

Several inflammatory processes of the bowel are characterized by an accumulation of eosinophils at inflammation sites. The mechanisms that govern mucosal infiltration with eosinophils are not fully understood. In this work, we studied the colorectal polyp-confined tissue containing eosinophils and we hypothesized that intestinal epithelial cells are the cell source of eotaxin-3 or CCL26, a potent chemoattractant for eosinophils. We analyzed colorectal polyps (n=50) from pediatric patients with rectal bleeding by H&E staining and eosin staining, and different pro-inflammatory cytokines were assessed by RT-qPCR and ELISA. IgE and CCL26 were investigated by RT-qPCR, ELISA and confocal microscopy. Finally, the intracellular signaling pathway that mediates the CCL26 production was analyzed using a kinase array and immunoblotting in human intestinal Caco-2 cell line. We found a dense cell agglomeration within the polyps, with a significantly higher frequency of eosinophils than in control adjacent tissue. IL-4 and IL-13 were significantly up-regulated in polyps and CCL26 was elevated in the epithelial compartment. Experiments with Caco-2 cells showed that the type-2 cytokine IL-13 increased STAT3 and STAT6 phosphorylation and eotaxin-3 secretion. The addition of the blocking antibody Dupilumab or the inhibitor Ruxolitinib to the cytokine-stimulated Caco-2 cells diminished the CCL26 secretion to basal levels in a dose-dependent manner. In conclusion, our findings demonstrate a high frequency of eosinophils, and elevated levels of type-2 cytokines and eotaxin-3 in the inflammatory stroma of colorectal polyps from pediatric patients. Polyp epithelial cells showed to be the main cell source of CCL26, and IL-13 was the main trigger of this chemokine through the activation of the STAT3/STAT6/JAK1-2 pathway. We suggest that the epithelial compartment actively participates in the recruitment of eosinophils to the colonic polyp-confined inflammatory environment.

Long-Term Dietary Patterns Are Reflected in the Plasma Inflammatory Proteome of Patients with Inflammatory Bowel Disease.

Diet plays an important role in the development and progression of inflammatory bowel disease (IBD, comprising Crohn’s disease (CD) and ulcerative colitis (UC)). However, little is known about the extent to which different diets reflect inflammation in IBD beyond measures such as faecal calprotectin or C-reactive protein. In this study, we aimed to unravel associations between dietary patterns and circulating inflammatory proteins in patients with IBD. Plasma concentrations of 73 different inflammation-related proteins were measured in 454 patients with IBD by proximity extension assay (PEA) technology. Food frequency questionnaires (FFQ) were used to assess habitual diet. Principal component analysis (PCA) was performed to extract data-driven dietary patterns. To identify associations between dietary patterns and plasma proteins, we used general linear models adjusting for age, sex, BMI, plasma storage time, smoking, surgical history and medication use. Stratified analyses were performed for IBD type, disease activity and protein intake. A high-sugar diet was strongly inversely associated with fibroblast growth factor-19 (FGF-19) independent of IBD type, disease activity, surgical history and deviance from recommended protein intake (false discovery rate (FDR) < 0.05). Conversely, a Mediterranean-style pattern was associated with higher FGF-19 levels (FDR < 0.05). A pattern characterised by high alcohol and coffee intake was positively associated with CCL11 (eotaxin-1) levels and with lower levels of IL-12B (FDR < 0.05). All results were replicated in CD, whereas only the association with FGF-19 was significant in UC. Our study suggests that dietary habits influence distinct circulating inflammatory proteins implicated in IBD and supports the pro- and anti-inflammatory role of diet. Longitudinal measurements of inflammatory markers, also postprandial, are needed to further elucidate the diet–inflammation relationship.

Disgust sensitivity is negatively associated with immune system activity in early pregnancy: Direct support for the Compensatory Prophylaxis Hypothesis

According to the Compensatory Prophylaxis Hypothesis (CPH), disgust may be considered a part of the behavioral immune system, adjusting as a function of immunocompetence. Early pregnancy involves modulation of a complex network of various immune-related factors, but only a few studies so far have focused on disgust sensitivity in pregnant women in the context of the CPH. This study aimed to examine associations between disgust sensitivity and immune activity indices, cytokine levels, and white blood cell (WBC) count in pregnant women. The sample included 78 women in the 1st trimester of pregnancy. Higher disgust sensitivity (Disgust Scale-Revised; DS-R) was significantly associated with decreased levels of IL-1β, IL-2 IL-4, IL-7, IL-17, Eotaxin, MCP-1 (MCAF), and RANTES in blood serum. This model explained 17.5% of the total DS-R score variability. Using the DS-R subscales, the Contamination disgust was significantly associated with levels of FGF basic, IFN-γ, IL-1β, IL-2, IL-4, IL-7, IL-17A, G-CSF, MCP-1 (MCAF), MIP-1α, PDGF-BB, and RANTES, and the Core disgust was significantly associated with levels of IL-1β, IL-2, IL-4, IL-7, IL-17A, Eotaxin, G-CSF, IP-10, MCP-1 (MCAF), PDGF-BB, and TNF-α. Disgust sensitivity was not associated with WBC count. Disgust may reflect and compensate for insufficient immune adaptation in early pregnancy, suggesting the potential clinical significance of this common prenatal symptom.

Systemic cytokine profiles in biliary atresia.

BackgroundInflammation and immune dysregulation persuade biliary duct injury in biliary atresia (BA), a leading cause of pediatric liver transplantation given lack of specific biomarkers. We aimed to determine associations between systemic cytokine profiles and clinical parameters in BA patients and to identify potential BA biomarkers.MethodsSystemic levels of 27 cytokines were measured in 82 BA patients and 25 healthy controls using a multiplex immunoassay. Relative mRNA expressions of candidate cytokines in 20 BA livers and 5 non-BA livers were assessed using quantitative real-time PCR.ResultsHigher levels of 17 cytokines including IL-1β, IL-6, IL-7, IL-8, IL-9, IL-2, IL-15, eotaxin, IP-10, MCP-1, MIP-1α, MIP-1β, G-CSF, IL-1ra, IL-4, IL-5, and IL-10 and lower levels of IFN-α and PDGF were significantly associated with BA. In BA patients, increased levels of IL-7, eotaxin, IP-10, and IL-13 were significantly associated with unfavorable outcomes including jaundice, fibrosis, and portal hypertension. Indeed, systemic levels of those cytokines were significantly correlated with clinical parameters indicating jaundice, fibrosis, and hepatic dysfunction in BA patients. Out of 27 cytokines, 4 (IL-8, IP-10, MCP-1, and PDGF) had potential as sensitive and specific biomarkers of BA. Of these, higher IL-8 levels were significantly associated with reduced survival of BA. In BA livers, relative mRNA expressions of IL-8, IP-10, and MCP-1 were significantly up-regulated.ConclusionsHigher levels of several cytokines including inflammatory cytokines, immunomodulatory cytokines, chemokines, and anti-inflammatory cytokines and lower levels of growth factors would reflect inflammatory and immune responses related to BA development. Among 27 cytokines, plasma IL-8 might have great potential as a diagnostic and prognostic biomarker for BA.

The Expression of Cytokine Profiles and Related Receptors in Idiopathic Inflammatory Myopathies.

Background: Cytokines play a vital role in the pathogenesis of idiopathic inflammatory myopathies (IIMs). Here, we investigated the expression of serum cytokine profiles in untreated IIMs and their correlations with clinical indicators, and further studied the expression of related cytokines receptors in IIMs. Methods: The Human 48-Plex Luminex assay for cytokines was performed in the serum of IIMs, including 93 untreated and 18 follow-up (39 samples) patients, and 32 healthy controls (HC). Mann-Whitney U test with bonferroni adjusted was used to identify the differentially expressed cytokines among groups. Celltalker software was used to identify the receptors of differentially expressed cytokines. The expression of receptors was further validated by published GEO datasets (muscle, blood and skin), RT-qPCR, western blot and flow cytometry. Results: The serum levels of Eotaxin, IL7, IL18, IP10, MCP1, MCSF, MIG and SCGFβ were elevated in the 93 untreated patients. Except for IL7, all other cytokines were decreased after treatment and their levels were positively correlated with clinical indices such as LDH, ESR, CRP, ALT, IgA, AST and IgG while negatively correlated with albumin and MMT8. According to the serum myositis-specific antibodies (MSAs), patients were classified into three groups: anti-ARS (Jo-1, OJ, EJ, PL7, PL12), anti-MDA5 positive, and anti-TIF1γ positive. Compared with HC, the levels of IP10 and MIG were increased in three groups. Moreover, IL18 and MSCF were increased in anti-ARS patients, and CTACK, Eotaxin, IL1Rα, IL7, IL18, MCP1, MCP3, MCSF and SCGFβ were elevated in anti-MDA5 patients. Twenty receptors of the 8 differentially expressed cytokines were matched by celltalker software, among them, IL18R1 and CCR1 were up-regulated in blood, muscle and skin of IIMs from the analysis of GEO published datasets. RT-qPCR and western blot further validated IL18R1 was upregulated in the muscle tissues of dermatomyositis. The number of IL18R1+CD4+ cells was increased while IL18R1+CD8+ cells was decreased in peripheral blood of anti-MDA5 patients. Conclusion: This study showed that cytokine profiles were significantly changed in IIMs, and different MSA groups had unique cytokine expression patterns. The levels of some cytokine were correlated with clinical indices. The IL18 receptor IL18R1 might play important roles in IIMs.

Polysaccharide-Rich Fractions from Ganoderma resinaceum (Ganodermataceae) as Chemopreventive Agents in N-Diethylnitrosamine-Induced Hepatocellular Carcinoma in Wistar Rats.

Hepatocellular carcinoma (HCC) is one of the most common and lethal diseases worldwide. Its treatment remains ineffective and the prognosis remains severe, thus favoring the emergence of a preventive approach. Mushroom-derived polysaccharides offer great opportunities because of their less toxicity and bioactivities. The present study aimed to investigate the chemopreventive effects of water-soluble polysaccharides from Ganoderma resinaceum on HCC. Two G. resinaceum polysaccharide-rich fractions (GRP I and GRP II) were obtained following hot water and alcohol precipitation. Their proteins, phenol compounds, and total neutral sugar content were assayed. The in vitro antiproliferative effect was assessed in MDA-MB 231, Hela, and HepG2 using the MTT assay. Further, for the in vivo study, seven groups of nine rats each received N-diethylnitrosamine (100 mg/kg BW), vehicle (NaCl 0.9%), doxorubicin (10 mg/kg BW), or G. resinaceum polysaccharides (125 and 250 mg/kg BW). Liver cancer initiation and progression was assessed by evaluating histomorphology of liver section, hepatic injury markers, hematology, cytokines/chemokines levels, and stress oxidative markers. GRP II presented higher protein and sugar and lower phenol compound content than GRP I. GRP exhibited CC50 of 340 and 261.7 in HepG2 cells after 48 h. Moreover, GRP I and GRP II (125 and 250 mg/kg) prevented the alteration of the histoarchitecture of the liver induced by the DEN. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP), proinflammatory cytokines (G-CSF, IFNγ, and TNFα), and chemokines (eotaxin and fractalkine) levels were significantly decreased in the GRP I- and GRP II-treated groups, while anti-inflammatory cytokines (IL-10 and IL-12p70) levels were increased. The antioxidant defense was also stimulated by reducing malondialdehyde (MDA) and nitric oxide (NO2) levels, increasing catalase (CAT) and superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. Our results indicate that GRP I exhibits chemopreventive effects by inhibiting cell proliferation and restoring liver architecture, antioxidant enzymes, and cytokines/chemokines balance.

Menthone Inhalation Alleviates Local and Systemic Allergic Inflammation in Ovalbumin-Sensitized and Challenged Asthmatic Mice.

Menthone is rich in Mentha × Piperita L. essential oil and it has anti-inflammatory properties; research shows that it is useful, via percutaneous absorption, in treating inflammation-related diseases. However, anti-allergic inflammatory effects of volatile menthone have not yet been used to treat allergic asthma, in vivo. We hypothesized that menthone inhalation may have anti-inflammatory and anti-allergic effects in patients with allergic asthma. Therefore, in our study, menthone inhalation was used to treat ovalbumin (OVA)-sensitized and challenged asthmatic mice. Allergic inflammation mediator changes in the lungs and airways, sera, splenocytes, and peritoneal macrophages of the mice were measured. Relative expression amounts of six receptor genes related to allergic inflammation of the lungs and airways were quantitated using a two-step real time quantitative polymerase chain reaction (qPCR). Results showed that menthone inhalation increased serum OVA-specific IgG2a/IgG1 and IgG2a/IgE ratios, increased Th1-type cytokine production in the bronchoalveolar lavage fluid, and decreased nitric oxide, protein, and eotaxin levels. Menthone inhalation inhibited mast cell and eosinophil degranulation, and chemokine (C-C motif) receptor 3 (Ccr3) gene expression amounts, but (relatively) increased Th1 cytokine secretion by splenocytes. Our results evidence that menthone inhalation alleviates local and systemic allergic inflammation in asthmatic mice.

Donor and Recipient Cytokine Profiles Predict Acute Rejection and Graft-Related Survival After Heart Transplantation

<h3>Purpose</h3> Heart transplant results have improved but primary graft dysfunction (PGD) and acute rejection remain obstacles for long-term survival. Donor and recipient inflammation may be involved in immune activation of the transplant, resulting in adverse consequences. Here, we investigated donor and recipient plasma and intragraft cytokine profiles and searched for predictive markers for unfavourable outcomes. <h3>Methods</h3> Perioperative donor and recipient plasma samples and myocardial biopsies of 84 heart transplants were analyzed. Plasma and intragraft cytokine levels were determined by multiplexed and next-generation sequencing platforms. The development of PGD, acute rejection, and graft-related survival up to 1 year after transplantation, were examined. Maximally selected rank statistics was used to determine the cytokine cut-off values for prediction of rejection or graft-related survival. <h3>Results</h3> Severe PGD was associated with early mortality and an increase in intragraft and plasma proinflammatory cytokines. Cytokine network analysis identified interleukins -6, -8, -10, and -18 as key players during reperfusion injury. Low donor plasma levels of IL-1Ra, MIF, MIP1a, and eotaxin increased the risk of ≥G2R rejection in the first year. High recipient preoperative and postoperative levels of various proinflammatory cytokines were linked with an increased risk of graft-related 1-year mortality. <h3>Conclusion</h3> Severe PGD was associated with a proinflammatory cytokine profile in the recipients. A high immunological risk score based on donor plasma cytokines predicted acute rejection, while recipient cytokine-based risk scores predicted graft-related 1-year mortality. Our results suggest that these predictive markers could potentially be used to tailor recipient immunosuppression and to improve organ allocation.

Inflammatory and contractile profile in LPS-challenged equine isolated bronchi: Evidence for IL-6 as a potential target against AHR in equine asthma

BackgroundAirway inflammation and airway hyperresponsiveness (AHR) are pivotal characteristics of equine asthma. Lipopolysaccharide (LPS) may have a central role in modulating airway inflammation and dysfunction. Therefore, the aim of this study was to match the inflammatory and contractile profile in LPS-challenged equine isolated bronchi to identify molecular targets potentially suitable to counteract AHR in asthmatic horses. MethodsEquine isolated bronchi were incubated overnight with LPS (0.1–100 ng/ml). The contractile response to electrical field stimulation (EFS) and the levels of cytokines, chemokines, and neurokinin A (NKA) were quantified. The role of capsaicin sensitive-sensory nerves, neurokinin-2 (NK2) receptor, transient receptor potential vanilloid type 1 receptors (TRPV1), and epithelium were also investigated. ResultsLPS 1 ng/ml elicited AHR to EFS (+238.17 ± 25.20% P < 0.001 vs. control). LPS significantly (P < 0.05 vs. control) increased the levels of IL-4 (+36.08 ± 1.62%), IL-5 (+38.60 ± 3.58%), IL-6 (+33.79 ± 2.59%), IL-13 (+40.91 ± 1.93%), IL-1β (+1650.16 ± 71.16%), IL-33 (+88.14 ± 8.93%), TGF-β (22.29 ± 1.03%), TNF-α (+56.13 ± 4.61%), CXCL-8 (+98.49 ± 17.70%), EOTAXIN (+32.26 ± 2.27%), MCP-1 (+49.63 ± 4.59%), RANTES (+36.38 ± 2.24%), and NKA (+112.81 ± 6.42%). Capsaicin sensitive-sensory nerves, NK2 receptor, and TRPV1 were generally involved in the LPS-mediated inflammation. Epithelium removal modulated the release of IL-1β, IL-33, and TGF-β. Only the levels of IL-6 fitted with AHR to a wide range of EFS frequencies, an effect significantly (P < 0.05) inhibited by anti-IL-6 antibody; exogenous IL-6 induced significant (P < 0.05) AHR to EFS similar to that elicited by LPS. ConclusionTargeting IL-6 with specific antibody may represent an effective strategy to treat equine asthma, especially in those animals suffering from severe forms of this disease.

Different levels of EGF, VEGF, IL-6, MCP-1, MCP-3, IP-10, Eotaxin and MIP-1α in the adipose-derived stem cell secretome in androgenetic alopecia.

Hair folliculogenesis and hair growth mediated by the secretory properties of white adipocytes may pave the way for the adipose-derived (AD) regenerative therapy for androgenetic alopecia (AGA). Quantitative and qualitative secretome profiling of AD stem cells (ADSCs) from different zones of hair growth in patients with AGA were analysed. 1-mm punch samples of adipose tissue associated with hair follicles, of three scalp areas (balding, non-balding and transition zones) and one periumbilical sample, were used for ADCS isolation. The ADCS secretome was analysed in conditioned media using a 41plex assay. Among the thirty-five signalling proteins analysed, the levels of VEGF, EGF, IL-6, Eotaxin, MCP-3, IFNγ-inducible protein-10 and MIP-1α were higher in the balding zone compared with the non-balding and periumbilical zones. In contrast, MCP-1 was the lowest in the balding zone in comparison with the other zones. The observed differences in the secretome suggest crosstalk between angiogenic and inflammatory processes underlying AGA aetiology and may prove relevant in both the diagnosis of AGA and the application of ADSC secretome for AGA treatment.

Clinical Aspect of Cytokines and Chemokines in Liver Transplant

The objective of this prospective observational study was to determine whether a transplanted liver graft releases proinflammatory cytokines and chemokines on reperfusion and to determine the relationship between these molecules and subsequent ischemic reperfusion injury and acute kidney injury. Blood samples from 66 consecutive patients undergoing liver transplant were analyzed for cyto- and chemokines at different time frames before and after liver transplant. Ischemic reperfusion injury was defined based on the peak levels of arginine transaminase and divided into 3 groups: mild, moderate, and severe. Acute kidney injury was defined according to the latest Kidney Disease: Improving Global Outcomes classification. For more than 40 different cyto/chemokines and growth factors, a certain pattern of expression was observed in all patients with ischemic reperfusion injury. G-SCF, IP10, and HSP90a were significantly elevated in all patients with ischemic reperfusion injury. On the other hand, eotaxin and MCP1 levels were markedly elevated in patients without ischemic reperfusion, suggesting a possible cytoprotective effect. We identified cold ischemia, macrosteatosis > 30%, postreperfusion syndrome, and postoperative use of 2 or more vasoactive agents as independent risk factors for ischemic reperfusion injury. Ischemia reperfusion injury is accompanied by distinct innate and adaptive immune cytokine signatures before and after transplant. It can be used for therapeutic intervention with goal to improve post-transplant graft outcomes.

PM2.5 aggravates airway inflammation in asthmatic mice: activating NF-κB via MyD88 signaling pathway

ABSTRACT The role of PM2.5 in the bronchial asthma remains unclear. In this study, the deficient mice of TLR4-/-, TLR2-/- and MyD88 -/- were used to establish asthma model. The effects of PM2.5 on the inflammatory response in lung tissue of these mice were observed. PM2.5 increased alveolar macrophages and neutrophils, up-regulated the IL-12 and KC expression in WT mice, but down-regulated their levels in TLR2 -/-, TLR4 -/- and MyD88 -/- mice. OVA+PM2.5 stimulated neutrophil count in WT mice, but it decreased in TLR2 -/- and TLR4 -/- mice. OVA+PM2.5 also increased the Eotaxin, IL-5, IL-13 and MCP-3 expression levels, and OVA specific IgE and IgG1 in serum also increased in WT group. PM2.5 may activate NF-κB through the TLR2/TLR4/MyD88 signaling pathway and aggravate allergic inflammation of lung in asthmatic mice. The microelements in PM2.5 granules, such as lipopolysaccharide, may be an important factor in the high incidence of asthma.

Difference of Serum Cytokine Profile in Allergic Asthma Patients According to Disease Severity.

PurposeAllergic asthma is a heterogeneous disease with complex underlying mechanisms. Cytokines are key mediators in immune system and potential indicators of disease status. The aim of this study is to compare the difference of serum cytokine profile in allergic asthma patients with different disease severity and explore candidate biomarkers for disease monitoring and targeting therapeutic agents.Patients and MethodsA total of 40 allergic asthmatics (mild, n=22; moderate-to-severe, n=18) were included in this study. Serum samples, lung function and exhaled nitric oxide data were collected from each subject. A Meso Scale Discovery (MSD) electrochemiluminescence platform was applied to access serum levels of 33 cytokines. Serum cytokine profile was compared between mild and moderate-to-severe allergic asthmatics, and the correlation between serum cytokine levels, lung function and exhaled nitric oxide were analyzed.ResultsModerate-to-severe allergic asthmatics displayed higher levels of eotaxin-1, eotaxin-2, MCP-1, MCP-2, MCP-3, YKL-40 and lower IL-23, IL-31 and TRAIL in serum in comparison with mild allergic asthmatics. Serum YKL-40, eotaxin-1 and MCP-1 had the best ability to discriminate mild and moderate-to-severe allergic asthmatics, with an AUC of 0.833, 0.811 and 0.760. Serum IP-10 was positively correlated with FeNO levels, while FnNO displayed a strong positive correlation with serum IL-25.ConclusionCompared with mild allergic asthmatics, significant increase in serum eotaxin-1, eotaxin-2, MCP-1, MCP-2, MCP-3, YKL-40 and decrease in serum IL-23, IL-31 and TRAIL was noted in moderate-to-severe allergic asthmatics. YKL-40, eotaxin-1 and MCP-1 might be candidate biomarkers in reflecting severity in allergic asthma patients.

Effect of Multiple Sclerosis Cerebrospinal Fluid and Oligodendroglia Cell Line Environment on Human Wharton's Jelly Mesenchymal Stem Cells Secretome.

Multiple sclerosis (MS) is a neurological disorder of autoimmune aetiology. Experimental therapies with the use of mesenchymal stem cells (MSCs) have emerged as a response to the unmet need for new treatment options. The unique immunomodulatory features of stem cells obtained from Wharton’s jelly (WJ-MSCs) make them an interesting research and therapeutic model. Most WJ-MSCs transplants for multiple sclerosis use intrathecal administration. We studied the effect of cerebrospinal fluid (CSF) obtained from MS patients on the secretory activity of WJ-MSCs and broaden this observation with WJ-MSCs interactions with human oligodendroglia cell line (OLs). Analysis of the WJ-MSCs secretory activity with use of Bio-Plex Pro™ Human Cytokine confirmed significant and diverse immunomodulatory potential. Our data reveal rich WJ-MSCs secretome with markedly increased levels of IL-6, IL-8, IP-10 and MCP-1 synthesis and a favourable profile of growth factors. The addition of MS CSF to the WJ-MSCs culture caused depletion of most proteins measured, only IL-12, RANTES and GM-CSF levels were increased. Most cytokines and chemokines decreased their concentrations in WJ-MSCs co-cultured with OLs, only eotaxin and RANTES levels were slightly increased. These results emphasize the spectrum of the immunomodulatory properties of WJ-MSCs and show how those effects can be modulated depending on the transplantation milieu.

Inflammatory Markers, Pulmonary Function, and Clinical Symptoms in Acute COVID-19 Among Non-Hospitalized Adolescents and Young Adults.

SummaryMild, subacute COVID-19 in young people show inflammatory enhancement, but normal pulmonary function. Inflammatory markers are associated with age and male sex, whereas clinical symptoms are associated with age and female sex, but not with objective disease markers.BackgroundCoronavirus Disease 2019 (COVID-19) is widespread among adolescents and young adults across the globe. The present study aimed to compare inflammatory markers, pulmonary function and clinical symptoms across non-hospitalized, 12 – 25 years old COVID-19 cases and non-COVID-19 controls, and to investigate associations between inflammatory markers, clinical symptoms, pulmonary function and background variables in the COVID-19 group.MethodsThe present paper presents baseline data from an ongoing longitudinal observational cohort study (Long-Term Effects of COVID-19 in Adolescents, LoTECA, ClinicalTrials ID: NCT04686734). A total of 31 plasma cytokines and complement activation products were assayed by multiplex and ELISA methodologies. Pulmonary function and clinical symptoms were investigated by spirometry and questionnaires, respectively.ResultsA total of 405 COVID-19 cases and 111 non-COVID-19 controls were included. The COVID-19 group had significantly higher plasma levels of IL-1β, IL-4, IL-7, IL-8, IL-12, TNF, IP-10, eotaxin, GM-CSF, bFGF, complement TCC and C3bc, and significantly lower levels of IL-13 and MIP-1α, as compared to controls. Spirometry did not detect any significant differences across the groups. IL-4, IL-7, TNF and eotaxin were negatively associated with female sex; eotaxin and IL-4 were positively associated with age. Clinical symptoms were positively associated with female sex and age, but not with objective disease markers.ConclusionsAmong non-hospitalized adolescents and young adults with COVID-19 there was significant alterations of plasma inflammatory markers in the subacute stage of the infection. Still, pulmonary function was normal. Clinical symptoms were independent of inflammatory and pulmonary function markers, but positively associated with age and female sex.

LncRNA HCP5 Participates in the Tregs Functions in Allergic Rhinitis and Drives Airway Mucosal Inflammatory Response in the Nasal Epithelial Cells

Allergic rhinitis (AR) is an allergic disease characterized as (immunoglobulin, IgE)-mediated type I hypersensitivity disorder. Regulatory T cells (Tregs) play a crucial role in AR. In the present study, we aimed to investigate the mechanism of how Tregs are regulated by long noncoding RNA HCP5 and the regulatory role of HCP5 in IL-13-induced inflammatory response in nasal epithelial cells (NECs) from AR patients. Peripheral blood mononuclear cells (PBMCs) and NECs were obtained from collected blood samples and nasal epithelial tissues. CD4+ T cells and Tregs were purified using certain cell isolation kits from PBMCs and Tregs were also differentiated from CD4+ T cells using recombinant human IL-2 and TGF-β. The expression levels of HCP5, miR-16, ATXN2L, GM-CSF, eotaxin, and MUC5AC were detected by real-time PCR and western blot. The concentrations of inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). The interaction among HCP5, miR-16, and ATXN2L were verified by dual-luciferase reporter assay. lncRNA HCP5 expression dramatically downregulated in PBMCs, CD4+ T cells, Tregs, and nasal tissues of AR patients, as well as in IL-13-treated NECs. HCP5 promoted Tregs differentiation and proliferation via targeting miR-16/ATXN2L axis. Additionally, HCP5 inhibited IL-13-induced GM-CSF, eotaxin, and MUC5AC production in NECs. HCP5 sponged miR-16 and negatively regulated its expression, and miR-16 targeted ATXN2L and inhibition of miR-16 suppressed IL-13-induced GM-CSF, eotaxin, and MUC5AC expression. HCP5/miR-16/ATXN2L axis mediated Tregs proliferation and functions in AR. Besides, the regulation of IL-13-induced dysfunction of NECs by lncRNA HCP5 depended on miR-16/ATXN2L in the inflammatory response of AR.

Physical exercise is associated with a reduction in plasma levels of fractalkine, TGF-β1, eotaxin-1 and IL-6 in younger adults with mobility disability.

Mobility disability (MD) refers to substantial limitations in life activities that arise because of movement impairments. Although MD is most prevalent in older individuals, it can also affect younger adults. Increasing evidence suggests that inflammation can drive the development of MD and may need to be targeted for MD prevention. Physical exercise has anti-inflammatory properties and has been associated with MD prevention. However, no studies to date have examined whether exercise interventions affect the peripheral inflammatory status in younger adults with MD. To this end, we used blood samples from young and middle-aged adults with MD (N = 38; median age = 34 years) who participated in a 12-week intervention that included aerobic and resistance exercise training. A pre-post assessment of inflammatory biomarkers was conducted in plasma from two timepoints, i.e., before the exercise trial and at follow-up (3–7 days after the last exercise session). We successfully measured 15 inflammatory biomarkers and found that exercise was associated with a significant reduction in levels of soluble fractalkine, transforming growth factor beta 1 (TGF-β1), eotaxin-1 and interleukin (IL) 6 (corrected α = 0.004). We also found significant male-specific effects of exercise on (i) increasing IL-16 and (ii) decreasing vascular endothelial growth factor-A (VEGF-A). In line with our results, previous studies have also found that exercise can reduce levels of TGF-β1, eotaxin-1 and IL-6. However, our finding that exercise reduces plasma levels of fractalkine in younger adults with MD, as well as the sex-dependent findings, have not been previously reported and warrant replication in larger cohorts. Given the suggested role of inflammation in promoting MD development, our study provides additional support for the use of physical exercise as a treatment modality for MD.

Evaluation of the serum visfatin eotaxin and fetuin-A levels of patients with type 2 diabetes mellitus

Objective: The aim of this study was to determine the serum visfatin, eotaxin and fetuin-A levels in patients with normal BMI and overweight type 2 diabetes mellitus (T2DM).&#x0D; Material and Method: This study perform in 30 T2DM patients and in 20 healthy subjects. Test subjects were divided into four groups as two diabetics and two controls. Diabetics with a body mass index (BMI) of 26.2-29.9 kg/m2 were included in the overweight diabetic group (OD), and those with a body mass index of 20.9-24.9 kg/m2 were included in the normal BMI diabetic group (ND). The volunteers in the control group were also divided into two groups as overweight (OC) and normal BMI (NC). Smoking and alcohol users were not included in the study. In addition, patients with significant diabetic complications such as retinopathy, hypertension, neuropathy, renal failure, and cardiovascular disease were excluded from the study. The serum visfatin eotaxin and fetuin-A levels were measured using the ELISA method. The Mann-Whitney U test was used to compare the data of the groups, while Spearman’s analysis was applied for the correlations.&#x0D; Results: The visfatin levels of the OD and ND were significantly higher compared to those of their control groups (p