Eotaxin Levels Research Articles

Quantitative and qualitative analysis of stability for 16 serum immunoregulators over 50 freeze-thaw cycles.

To evaluate the reliability of data from the assay of bio-archived specimens, a 50-freeze-thaw-cycle (FTC) degradation study of fresh sera was conducted to test the stability of 16 immunoregulators. Twenty de-identified serum specimens were obtained from volunteers at United Health Services-Wilson Memorial Hospital. Specimens were stored at -20°C and underwent daily 1 h thawing and subsequent freezing for each FTC over 50 consecutive days. Immunoregulator concentrations were assessed via enzyme-linked immunosorbent assay (ELISA) in participant samples at 2 FTC (baseline), 25 FTC, and 50 FTC. Specific immunoregulators observed in the study were C-reactive protein (CRP), interleukin (IL)-1α, 4, 6, 8, 10, monocyte chemoattractant protein-1 (MCP-1, CCL2), monocyte chemoattractant protein-2 (MCP-2, CCL8), eotaxin-1, thymus-and-activation-regulated chemokine (TARC, CCL17), regulated on activation normal T-cell expressed and secreted (RANTES, CCL5), growth-regulated oncogene-alpha (GRO-α, CXCL1), small inducible cytokine A1 (I-309, CCL1), interferon-gamma (IFN-γ), interferon-gamma inducible protein-10 (IP-10, CXCL10), and tumor necrosis factor-alpha (TNF-α). Quantitative stability of serum immunoregulators: Serum CRP, IL-8, IL-10, IFN-γ, IP-10, and eotaxin-1 levels appear to be statistically equivalent from baseline to 50 FTC (p ≤ .05). Retention of patterns in serum immunoregulators: patterns across FTC were retained for TARC (age) and CRP, IFN-γ, and MCP-2 (sex). While the effect of multiple FTC on serum immunoregulator levels may not replicate prolonged freezer storage, the results of this study provide valuable information on the robustness of immunoregulators for research using bio-archived sera.

Relationship between serum IgA levels and low percentage forced expiratory volume in the first second in asthma

Objective: Immunoglobulin A (IgA) is suggested to have pathogenic effects in respiratory inflammatory diseases, including asthma. We aimed to analyze the relationship between serum IgA, and clinical indicators and biomarkers of asthma.Methods: This study was a post hoc analysis of the NHOM Asthma Study. In this study, serum IgA was measured using serum samples stored. We determined an association between the serum IgA level and clinical variables and biomarkers using multivariate linear regression and analyzed the differences in clinical indices between IgA high- and IgA low-asthma.Results: In this study, 572 patients with asthma were included in the final analysis. Lower percentage forced expiratory volume in the first second (%FEV1), higher serum eotaxin levels, lower serum ST2 levels, and higher serum MIP-1β levels, were independently and significantly associated with higher serum IgA levels among asthma patients by multivariate linear regression analysis (%FEV1, 95% confidence interval [CI], −8.18– −0.613, p < 0.05; eotaxin, 95% CI, 8.95–46.69, p < 0.001; ST2, 95% CI, −73.71– −7.37, p < 0.05; and MIP-1β, 95% CI, 1.47–18.71, p < 0.05). Furthermore, IgA high-asthma (serum IgA ≥ 238 mg/dL, n = 270) and IgA low-asthma (serum IgA < 238 mg/dL, n = 302) were compared separately. %FEV1 was significantly lower, the percentage of atopy was higher, and serum MIP-1β level was higher in IgA high-asthma.Conclusions: This study suggests that serum IgA may be involved in the worsening of asthma outcomes, as assessed by %FEV1 and enhanced inflammation via elevated serum MIP-1β.

Decreased IL-4 is the risk factor of depression in patients with Takayasu arteritis.

Depression is a common complication in Takayasu arteritis (TA). Disorders of the immune system play an important role in both diseases. This study aimed to clarify the feature of cytokines in TA patients with depression. In this cross-sectional study, serum cytokines were tested in 40 TA patients and 11 healthy controls using the Bio-Plex Magpix System (Bio-Rad®). The state of depression was measured by the Zung Self-Rating Depression Scale (SDS) in TA patients. Logistic regression analysis was performed to find the risk factors of depression in patients with TA. TA patients with depression had higher ESR, hsCRP, NIH, and ITAS.A than patients without depression (16.00 [10.00, 58.50]mm/H vs. 7.50 [4.50, 17.75]mm/H, p = 0.013; 7.60 [2.32, 46.52]mg/L vs. 0.71 [0.32, 4.37]mg/L, p = 0.001; 2.00 [2.00, 3.00] vs. 1.00 [0.00, 2.00], p = 0.007; 7.00 [4.00, 9.50] vs. 1.50 [0.00, 5.75], p = 0.012, respectively). Additionally, the lower age of onset and levels of IL-4, IL-13, eotaxin, and IP-10 were observed in the depressed group compared with the non-depressed (23.50 [19.25, 32.50]pg./ml vs. 37.00 [23.25, 42.50]pg./ml, p = 0.017; 2.80 [2.17, 3.18]pg./ml vs. 3.51 [3.22, 4.66]pg./ml, p < 0.001; 0.66 [0.60, 1.12]pg./ml vs. 1.04 [0.82, 1.25]pg./ml, p = 0.008; 46.48 [37.06, 61.75]pg./ml vs. 69.14 [59.30, 92.80]pg./ml, p = 0.001; 184.50 [138.23, 257.25]pg./ml vs. 322.32 [241.98, 412.60]pg./ml, p = 0.005, respectively). The lower level of IL-4 and age of onset were the independent risk factors for depression in TA patients (OR [95% CI] 0.124 [0.018, 0.827], p = 0.031; 0.870 [0.765, 0.990], p = 0.035, respectively). Our data suggested that lower cytokine levels, especially IL-4, might be involved in the development of TA patients with depression. Clinicians can probably use serum IL-4 level testing as a potential indicator of depression in TA.

Cognitive and immunological effects of yoga compared to memory training in older women at risk for alzheimer’s disease

Subjective cognitive decline (SCD) and mild cognitive impairment (MCI) accompanied by cerebrovascular risk factors (CVRFs) are known to increase the risk of developing dementia. Mind-body practices such as yoga and meditation, have been recognized as safe techniques with beneficial effects on cognitive functions in older adults at risk for cognitive decline. We conducted a randomized, controlled trial to assess the efficacy of Kundalini yoga training (KY) compared to memory enhancement training (MET) on mood and cognitive functioning in a group of older women with CVRFs and SCD (clinicaltrials.gov = NCT03503669). The KY intervention consisted of weekly, 60-min in-person classes with a certified instructor for 12 weeks, with a 12-min guided recording for daily homework practice at home. MET involved 12 weekly in-person group classes with 12-min daily homework exercises. Objective and subjective memory performance were the primary outcomes. Peripheral whole blood samples were collected at baseline, 12-weeks, and 24-weeks follow-up for RNA sequencing and cytokine/chemokine assays. A total of 79 patients (KY = 40; MET = 39) were randomized, and 63 completed the 24-week follow-up (KY = 65% completion rate; MET = 95%; χ2(1) = 10.9, p < 0.001). At 24-weeks follow-up, KY yielded a significant, large effect size improvement in subjective cognitive impairment measures compared to MET. KYOn a transcriptional level, at 12- and 24-week follow-up, KY uniquely altered aging-associated signatures, including interferon gamma and other psycho-neuro-immune pathways. Levels of chemokine eotaxin-1, an aging marker, increased over time in MET but not KY participants. These results suggest clinical and biological benefits to KY for SCD, linking changes in cognition to the anti-inflammatory effects of yoga.

Discovery of a novel cytokine signature for the diagnosis of autism spectrum disorder in young Arab children in Qatar.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by impaired social interaction and communication and the occurrence of stereotyped and repetitive behaviors. Several studies have reported altered cytokine profiles in ASD and hence may serve as potential diagnostic biomarkers of the disorder. This study aims to identify diagnostic biomarkers for ASD in a well-defined study cohort in Qatar. We measured the protein levels of 45 cytokines in the plasma samples of age- and gender-matched children (2-4 years) with ASD (n = 100) and controls (n = 60) using a Luminex multiplex assay. We compared the differences in the levels of these cytokines between the two study groups and then fitted the significantly altered cytokines into a logistic regression model to examine their diagnostic potential for ASD. We found elevated levels of IFN-γ, FGF-2, IL-1RA, and IL-13 and reduced levels of eotaxin, HGF, IL-1 alpha, IL-22, IL-9, MCP-1, SCF, SDF-1 alpha, VEGFA, and IP-10 in the plasma of children with ASD compared to controls. Furthermore, we observed that elevated levels of IFN-γ (odds ratio (OR) = 1.823; 95% (confidence interval) CI = 1.206, 2.755; p = 0.004) and FGF-2 (OR = 2.528; 95% CI = 1.457, 4.385; p < 0.001) were significantly associated with increased odds of ASD, whereas reduced levels of eotaxin (OR = 0.350; 95% CI = 0.160, 0.765; p = 0.008) and HGF (OR = 0.220; 95% CI = 0.070, 0.696; p = 0.010) were significantly associated with lower odds of ASD relative to controls. The combination of these four cytokines revealed an area under the curve (ROC-AUC) of 0.829 (95% CI = 0.767, 0.891; p < 0.001), which demonstrates the diagnostic accuracy of the four-cytokine signature. Our results identified a panel of cytokines that could discriminate between children with ASD and controls in Qatar. In addition, our findings support the predominance of a Th1 immune phenotype in ASD children and emphasize the need to validate these results in larger populations.

Fuch's Endothelial Corneal Dystrophy in Cataract Patients Is Associated with Elevated Levels of Inflammatory Chemokines, but Not Growth Factors, in the Aqueous Humor.

The study investigated a profile of chemokines and growth factors in the aqueous humor (AH) of eyes with Fuch's endothelial corneal dystrophy (FECD) and cataracts in comparison with cataract patients as a control group. A total of 52 AH samples (26 FECD + cataract and 26 cataract/control) were collected before cataract surgery. None of the patients had any clinically apparent inflammation at the time of AH collection. The AH levels of MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β(CCL4), RANTES (CCL5), eotaxin (CCL11), IP-10 (CXCL10), FGF basic, G-CSF, GM-CSF, PDGF-bb, and VEGF were compared between the groups. The analyses were performed using the Bio-Plex 200 System from Bio-Rad. Among the studied parameters, the AH levels of RANTES, eotaxin, and IP-10 significantly increased in the FECD + cataract eyes, compared with the cataract controls (p < 0.05). Elevated levels of the RANTES, Eotaxin, and IP-10 indicate more intense inflammation in the eyes of patients in the FECD + cataract group. Moreover, these factors exhibit potential as predictive biomarkers for early detection of FECD in cataract patients. The discovery of elevated concentrations of biochemical markers in a patient, who has not yet received a clinical diagnosis, may suggest the need for heightened observation of the other eye to monitor the potential development of FECD.

Mechanisms of Er Chen Tang on Treating Asthma Explored by Network Pharmacology and Experimental Verification.

The aim of this study is to explore the active ingredients of ECT and their targets for asthma and investigate the potential mechanism of ECT on asthma. Firstly, the active ingredients and target of ECT were screened for BATMAN and TCMSP, and functional analysis was done via DAVID. Then, the animal model was induced by ovalbumin (OVA) and aluminum hydroxide. Eosinophil (EOS) counts, EOS active substance Eosinophilic cationic protein (ECP) and eotaxin levels were detected following the instruction. Pathological changes in lung tissue were examined by H&E staining and transmission electron microscopy. Interleukin (IL-4, IL-10, IL-13, TNF-α), TIgE and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA. Finally, the protein expression of the TGF-β / STAT3 pathway to lung tissue was detected by Western Blot. A total of 450 compounds and 526 target genes were retrieved in Er Chen Tang. Functional analysis indicated that its treatment of asthma was associated with inflammatory factors and fibrosis. In the animal experiment, the results showed that ECT significantly regulated inflammatory cytokine (IL-4, IL-10, IL-13, TNF-α) levels in (P<0.05, P<0.01, reduced EOS number (P<0.05) and also ECP and Eotaxin levels in the blood (P<0.05) in BALF and/or plasma. Bronchial tissue injury was obviously improved on ECT treatment. Associated proteins in TGF-β / STAT3 pathway were significantly regulated by ECT (P<0.05). This study originally provided evidence that the Er Chen Tang was effective in the treatment of asthma symptoms, and its underlying mechanism might be the regulation of inflammatory factor secretion and the TGF-β/STAT3 signaling pathway.

Elevated MIF identified by multiple cytokine analyses facilitates macrophage M2 polarization contributing to postoperative recurrence in chronic rhinosinusitis with nasal polyps.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by tissue heterogeneity and high postoperative recurrence risk. This study aims to employ cytokine analyses to identify serum biomarkers associated with postoperative CRSwNP recurrence and elucidate underlying recurrent mechanisms. A prospective cohort study was conducted on CRSwNP patients undergoing functional endoscopic sinus surgery. Serum and tissue samples were collected and analyzed for multiple cytokines. Participants were followed for 3 years and categorized into recurrent and non-recurrent groups. Cytokine profiles were compared, and potential markers for recurrence were further assessed. Macrophage migration inhibitory factor (MIF) expression in macrophages was modulated, and their polarization and cytokine secretion were assessed. In the discovery cohort (21 recurrent and 40 non-recurrent patients), circulating cytokine profiles differed significantly, with 8 cytokines showing differential expression between the two groups. Among them, serum eotaxin, MIF, RANTES, and TRAIL exhibited promise in predicting recurrence. In the validation cohort (24 recurrent and 44 non-recurrent patients), serum eotaxin, MIF, and TRAIL levels were higher in recurrent cases. Tissue MIF was elevated in recurrent cases and had a strong predictive value for recurrence. Moreover, tissue MIF was co-expressed with CD206 in recurrent cases. Mechanistically, MIF overexpression promoted macrophage M2 polarization and TGF-β, CCL-24, and MIF secretion, and MIF recombinant protein facilitated M2 polarization, and TGF-β1 and CCL-24 production, contributing to CRSwNP recurrence. Serum-specific cytokine signatures were associated with postoperative recurrence risk in CRSwNP. Elevated MIF enhanced macrophage M2 polarization and cytokine secretion, contributing to the recurrent mechanisms of CRSwNP.

Evaluate the Levels of Serum Eotaxin-1, Myelin Basic Protein, and Some Immunological and Biochemical Markers in Iraqi Patients with Multiple Sclerosis

Evaluate the Levels of Serum Eotaxin-1, Myelin Basic Protein, and Some Immunological and Biochemical Markers in Iraqi Patients with Multiple Sclerosis

Changes in chemokine and growth factor levels may be useful biomarkers for monitoring disease severity in COVID-19 patients; a pilot study.

The aim of the present study was to assess differences in the serum levels of chemokines and growth factors (GFs) between COVID-19 patients and healthy controls. The diagnostic utility of the analyzed proteins for monitoring the severity of the SARS-CoV- 2 infection based on the patients' MEWS scores was also assessed. The serum levels of chemokines and growth factors were analyzed in hospitalized COVID-19 patients (50 women, 50 men) with the use of the Bio-Plex Pro™ Human Cytokine Screening Panel (Biorad) and the Bio-Plex Multiplex system. The study demonstrated that serum levels of MIP-1α, RANTES, Eotaxin, CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, SCGF-β, G-CSF, M-CSF, SCF, MIF, LIF, and TRAIL were significant higher in COVID-19 patients than in the control group. The concentrations of CTACK, GRO-α, IP-10, MIG, basic-FGF, HGF, PDGF- BB, GM-CSF, SCF, LIF, and TRAIL were higher in asymptomatic/mildly symptomatic COVID-19 patients (stage 1) and COVID-19 patients with pneumonia without respiratory failure (stage 2). The receiver operating characteristic (ROC) analysis revealed that IP-10, MIF, MIG, and basic-FGF differentiated patients with COVID-19 from healthy controls with the highest sensitivity and specificity, whereas GM-CSF, basic-FGF, and MIG differentiated asymptomatic/mildly symptomatic COVID-19 patients (stage 1) from COVID-19 patients with pneumonia without respiratory failure (stage 2) with the highest sensitivity and specificity. MIG, basic-FGF, and GM-CSF can be useful biomarkers for monitoring disease severity in patients with COVID-19.

Changes in Cytokine Levels in Patients with Severe Fever with Thrombocytopenia Syndrome Virus.

To characterize the cytokine profile of patients with severe fever with thrombocytopenia syndrome (SFTS) in relation to disease severity. 60 laboratory-confirmed SFTS patients and 12 healthy individuals from multi-centers in Shandong Province of China were included, and all patients were divided into fatal patients (9) and recovered patients (51) due to their final outcomes. Multiplex-microbead immunoassays were conducted to estimate levels of 27 cytokines in the sera of patients and controls. The results showed that levels of IL-2, IL-4, IL-6, IL-7, IL-8, IL-15, IL-1RA, G-CSF, GM-CSF, IFN-γ, TNF-α, basic FGF, PDGF-BB, RANTES, IP-10, MIP-1α, MIP-1β, MCP-1, and Eotaxin differed significantly among the SFTS fatal patients, recovered patients, and the healthy controls (all p<0.05). Compared to the healthy controls, the fatal patients and recovered patients had reduced levels of IL-2, IL-4, IL-7, PDGF-BB, RANTES, and Eotaxin, while the levels of PDGF-BB and RANTES were significantly lower in fatal patients compared to recovered patients. The increasing levels of IL-6, IL-8, IL-15, IL-1RA, G-CSF, GM-CSF, IFN-γ, TNF-α, basic FGF, IP-10, MIP-1α, MIP-1β, and MCP-1 were observed in fatal patients (all p<0.05), and the levels of IL-6, IP-10, MIP-1α, and MCP-1 were significantly higher than other two groups. The Spearman correlation analysis indicated a positive correlation between platelet count and PDGF-BB levels (p<0.05), while the white blood cell count had a negative correlation with MIP-1 level (p<0.05). The research exhibited that the SFTS virus (SFTSV) caused an atypical manifestation of cytokines. The levels of IL-6, IP-10, MIP-1α, and MCP-1 had been observed a positive association with the severity of the illness.

Urine biomarker could be a useful tool for differential diagnosis of a lower urinary tract dysfunction.

A precision diagnosis of lower urinary tract dysfunctions (LUTD) such as bladder outlet obstruction, detrusor overactivity (DO), interstitial cystitis/bladder pain syndrome (IC/BPS), dysfunctional voiding (DV), or detrusor underactivity (DU) needs invasive videourodynamic study. Exploring non-invasive tools to help screening LUTD is necessary for clinicians in their daily practice. This article reviews recently clinical studies of using urinary inflammatory proteins and oxidative stress biomarkers in the identification of specific LUTD among men and women with lower urinary tract symptoms (LUTS). Some important findings have been reported: (1) Using urine chemokines CXCL-1 and interleukin-8 (IL-8), we may discriminate overactive bladder (OAB) symptoms in women between DO and urinary tract infection. (2) Urinary levels of oxidative stress biomarkers such as 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane have a potential being used as a tool to identify women with mixed DO and stress urinary incontinence. (3) Urine levels of total antioxidant capacity (TAC), and prostaglandin E2 (PGE2) are positively correlated with voiding detrusor pressure in patients with DU. (4) Urine levels of brain-derived neurotrophic factor (BDNF) and PGE2 were significantly higher in the DU patients with detrusor function recovery. (5) Women with DV had higher urinary levels of tumor necrosis factor-alpha (TNF-α) and 8-OHdG, and urinary IL-2 level was significantly lower. (6) Urine level of 8-isoprostane was higher in the patients with idiopathic DO and neurogenic DO. (7) Higher urine cytokine levels of monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted (RANTES), CXCL-10, IL-7, and eotaxin-1 in patients with IC/BPS than controls. (8) The urine levels of IL-8, CXCL-10, BDNF, IL-6, and RANTES were significantly higher in patients with Hunner's IC than non-Hunner's IC. (9) Male patients with IC/BPS had a significantly higher level of eotaxin, MCP-1, TNF-α, 8-OHdG, and TAC. Combining a higher eotaxin and a higher TNF-α can provide a satisfactory diagnostic value in discriminating IC/BPS from other LUTD in men. These studies provide evidence that measurement of cluster of urine biomarkers could be used as a diagnostic tool to differentiate different LUTD in patients with similar LUTS.

Successful use of dupilumab for egg-induced eosinophilic gastroenteritis with duodenal ulcer: a pediatric case report and review of literature

BackgroundNon-esophageal eosinophilic gastrointestinal disorder (non-EoE-EGID) is a rare disease in which eosinophils infiltrate parts of the gastrointestinal tract other than the esophagus; however, the number of patients with non-EoE-EGID has been increasing in recent years. Owing to its chronic course with repeated relapses, it can lead to developmental delays due to malnutrition, especially in pediatric patients. No established treatment exists for non-EoE-EGID, necessitating long-term systemic corticosteroid administration. Although the efficacy of dupilumab, an anti-IL-4/13 receptor monoclonal antibody, for eosinophilic esophagitis, has been reported, only few reports have demonstrated its efficacy in non-EoE EGIDs.Case presentationA 13-year-old boy developed non-EoE-EGID with duodenal ulcers, with chicken eggs as the trigger. He was successfully treated with an egg-free diet, proton pump inhibitors, and leukotriene receptor antagonists. However, at age 15, he developed worsening upper abdominal pain and difficulty eating. Blood analysis revealed eosinophilia; elevated erythrocyte sedimentation rate; and elevated levels of C-reactive protein, total immunoglobulin E, and thymic and activation-regulated chemokines. Upper gastrointestinal endoscopy revealed a duodenal ulcer with marked mucosal eosinophilic infiltration. Gastrointestinal symptoms persisted even after starting systemic steroids, making it difficult to reduce the steroid dose. Subcutaneous injection of dupilumab was initiated because of comorbid atopic dermatitis exacerbation. After 3 months, the gastrointestinal symptoms disappeared, and after 5 months, the duodenal ulcer disappeared and the eosinophil count decreased in the mucosa. Six months later, systemic steroids were discontinued, and the duodenal ulcer remained recurrence-free. The egg challenge test result was negative; therefore, the egg-free diet was discontinued. Blood eosinophil count and serum IL-5, IL-13, and eotaxin-3 levels decreased after dupilumab treatment. The serum levels of IL-5 and eotaxin-3 remained within normal ranges, although the blood eosinophil counts increased again after discontinuation of oral prednisolone.ConclusionsSuppression of IL-4R/IL-13R-mediated signaling by dupilumab may improve abdominal symptoms and endoscopic and histologic findings in patients with non-EoE-EGID, leading to the discontinuation of systemic steroid administration and tolerance of causative foods.

Study of aqueous humour inflammatory mediators’ levels in a cohort of Egyptian patients with diabetic macular oedema

BackgroundThe aim was to study aqueous humour inflammatory mediators’ levels in a cohort of Egyptian patients with diabetic macular oedema (DMO).MethodsThis was a case-control prospective study conducted on 2 groups: 25 eyes of 22 (11 females) patients seeking treatment for DMO as patients group, and 10 eyes of 10 (4 females) cataract patients as a control group. Aqueous humour was aspirated before intravitreal injection (patients’ group) or cataract surgery (control group). Inflammatory mediators in aqueous humour were measured using a multiplex bead immunoassay kit of 27 pre-mixed cytokines.ResultsEotaxin, interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein-1 (MCP-1/CCL2) and interleukin-8 (IL-8/CXCL8) were found significantly higher in patients’ group compared to control group (p = 0.043, 0.037, 0.001, 0.015 respectively). On the contrary, interferon-gamma (IFN-gamma) and granulocyte colony-stimulating factor (G-CSF) were found significantly higher in control group than patients’ group (p = 0.003, 0.019 respectively). Basic fibroblast growth factor (Basic-FGF/FGF-2) and interleukin-1 receptor antagonist (IL-1ra) were found higher (but not statistically significant) in controls (p = 0.100 and 0.070 respectively). Additionally, a negative and significant correlation was found between Eotaxin level in aqueous humour and central macular thickness.ConclusionsSome mediators might be implicated in the pathogenesis of DMO either augmenting or suppressing role. Eotaxin, IP-10, MCP-1 and IL-8 might have a role in cases not responding to standard anti-vascular endothelial growth factor (VEGF) therapy. IL-1ra might have a protective role; therefore, the effectiveness of intravitreal injection of IL-1ra homologue needs to be studied in future clinical trials.

Cytokine Profiles of Chronic Urticaria Patients and The Effect of Omalizumab Treatment.

Cytokines are key mediators in immunological and inflammatory conditions, including chronic spontaneous urticaria (CSU). To investigate Th1, Th2, and Th17 cytokine profiles in CSU and to evaluate the possible effect of omalizumab treatment. Patients who were followed up for CSU, as well as healthy volunteers, were included in the study. To assess urticaria activity, the 7-day-Urticaria Activity Score (UAS-7), the Urticaria Control Test (UCT), and the Chronic Urticaria Quality of Life Questionnaire (CU-QoL) were filled. Serum levels of IL-6, IL-17, IL-31, eotaxin, RANTES, TNF-α, and TSLP were analyzed by ELISA and compared in CSU and control groups. The patients were analyzed in two groups as the omalizumab group and the non-omalizumab group based on their treatment status. Total IgE, ESR, CRP, RANTES, and TNF-a were significantly different in the overall comparison of the three groups: CSU-receiving omalizumab, CSU-not receiving omalizumab, and control groups (P <0.01, 0.015, <0.01, <0.01 and <0.01 respectively). Total IgE, CRP, RANTES, and TNF-α values were similar in those who received and did not receive omalizumab, yet these biomarkers were significantly higher in both groups than in the control group (P < 0.05). Statistical significance in ESR was observed only between the CSU-receiving omalizumab group and the control group (P = 0.01). Within the CSU patients, there was a slight but significant correlation between UCT and TNF-α (P = 0.008, r = 0.32) and IL-17 (P = 0.06, r = 0.33) levels. The investigated cytokine profile in CSU patients may differ from healthy controls, particularly with the higher levels of RANTES and TNF-α, and omalizumab treatment does not seem to affect that profile in CSU patients.

Efficacy of GV1001 with gemcitabine/capecitabine in previously untreated patients with advanced pancreatic ductal adenocarcinoma having high serum eotaxin levels (KG4/2015): an open-label, randomised, Phase 3 trial

BackgroundThe TeloVac study indicated GV1001 did not improve the survival of advanced pancreatic ductal adenocarcinoma (PDAC). However, the cytokine examinations suggested that high serum eotaxin levels may predict responses to GV1001. This Phase III trial assessed the efficacy of GV1001 with gemcitabine/capecitabine for eotaxin-high patients with untreated advanced PDAC.MethodsPatients recruited from 16 hospitals received gemcitabine (1000 mg/m2, D 1, 8, and 15)/capecitabine (830 mg/m2 BID for 21 days) per month either with (GV1001 group) or without (control group) GV1001 (0.56 mg; D 1, 3, and 5, once on week 2–4, 6, then monthly thereafter) at random in a 1:1 ratio. The primary endpoint was overall survival (OS) and secondary end points included time to progression (TTP), objective response rate, and safety.ResultsTotal 148 patients were randomly assigned to the GV1001 (n = 75) and control groups (n = 73). The GV1001 group showed improved median OS (11.3 vs. 7.5 months, P = 0.021) and TTP (7.3 vs. 4.5 months, P = 0.021) compared to the control group. Grade >3 adverse events were reported in 77.3% and 73.1% in the GV1001 and control groups (P = 0.562), respectively.ConclusionsGV1001 plus gemcitabine/capecitabine improved OS and TTP compared to gemcitabine/capecitabine alone in eotaxin-high patients with advanced PDAC.Clinical trial registrationNCT02854072.

Water extract of Pingchuan formula ameliorated murine asthma through modulating metabolites and gut microbiota

BackgroundPingchuan formula is a traditional Chinese herbal prescription for asthma, but its components and underlying mechanisms remain unclear. Here, we evaluated its anti-asthmatic actvity and regulatory effects on the gut microbiota in mice based on the traditional Chinese medicine Zang-Fu theory, which proposed the exterior–interior relationship between the lung and the large intestine. MethodsMouse model withovalbumin (OVA)-induced asthma was used to assess the protective effect of the water extract of Pingchuan formula (PC). The chemical compounds of PC and mouse serum metabolites were identified by Ultraperformance liquid chromatography-Q Exactive HF-X spectrometry. Gut microbiota was evaluated by 16 S rRNA gene sequencing. The gut microbiota was depleted with a broad-spectrum antibiotic mixture (Abx) to explore whether it plays a role in the protective effects of PC. ResultsPC mainly contains phenols, flavonoids, alkaloids, carboxylic acids, and their derivatives. PC attenuated OVA-induced asthma in mice by alleviating inflammatory infiltration, indicated by decreased levels of IL-18, IL-6, IL-4, and Eotaxin in lung tissues. PC treatment altered the serum metabolites and affected the pyrimidine pathway. In addition, our results showed that acacetin and abscisic acid were the key serum metabolites PC treatment changed the composition of gut microbiota by increasing the relative abundance of Clostridia_UCG_014 and Akkermansia while decreasing Blautia, Barnesiella, and Clostridium_Ⅲ at the genus level. Importantly, the Abx treatment partly abolished the anti-asthmatic effect of PC. ConclusionWe demonstrated that PC could alleviate OVA-induced asthma in mice and protect against inflammatory infiltration in lungs via modulating the serum metabolites and gut microbiota, thereby providing a new reference for the therapeutic effect of PC.

HDAC3-mediated lncRNA ZFAS1 inhibited IL-13-induced secretion of proinflammatory cytokines in nasal epithelial cells by regulating the miR-7-5p/SIRT1 pathway.

Allergic rhinitis (AR) is a disease that is difficult to cure and accompanies the patient's life. Proinflammatory cytokines (GM-CSF and eotaxin) and MUC5AC are key mediators promoting AR progression. Herein, the function of lncRNA ZFAS1 in AR was investigated. Nasal epithelial cells (NECs) were subjected to 50ng/mL IL-13 for 24h to construct an AR cell model. The mRNA and protein expressions were assessed using qRT-PCR and western blot. The levels of GM-CSF, eotaxin, IL-1β, IL-6, TNF-α and MUC5AC in cell supernatant were examined by ELISA. The binding relationships between HDAC3, ZFAS1, miR-7-5p and SIRT1 were analysed using dual luciferase reporter or ChIP assays. Herein, our results displayed that ZFAS1 and SIRT1 were lowly expressed in AR, while miR-7-5p and HDAC3 were highly expressed. Functional experiments displayed that ZFAS1 overexpression suppressed IL-13-induced proinflammatory cytokines and mucin production in NECs. The highly expressed HDAC3 in AR inhibited ZFAS1 expression by binding with ZFAS1 promoter. In addition, our experiments revealed that ZFAS1 targeted miR-7-5p, and miR-7-5p targeted SIRT1. As expected, miR-7-5p overexpression or SIRT1 silencing abrogated ZFAS1 upregulation's repression on IL-13-induced proinflammatory cytokines and MUC5AC secretory levels in NECs. ZFAS1 suppressed proinflammatory cytokines, inflammatory cytokines, and MUC5AC secretory levels in AR by regulating the miR-7-5p/SIRT1 axis. Thus, our work suggested that ZFAS1 might serve as a novel target for AR treatment and prevention.

Biomarkers for predicting immune reconstitution inflammatory syndrome in dipeptidyl peptidase‐4 inhibitor‐associated bullous pemphigoid: A retrospective observational study with a case series

AbstractBackgroundThe prognosis of dipeptidyl peptidase‐4 inhibitor‐associated bullous pemphigoid (DPP‐4i‐BP) is variable, with some cases showing spontaneous remission after drug cessation and others showing worsening BP or developing infectious complications, termed infectious immune reconstitution inflammatory syndrome (IRIS), after DPP‐4i cessation. We recently demonstrated that the neutrophil‐to‐lymphocyte ratio measured at baseline and during treatment predicts the eventual development of infectious IRIS.ObjectivesTo identify key molecular immune parameters that correlate with, and potentially shape, subsequent immune responses after DPP‐4i cessation.MethodsThis retrospective observational study examined DPP‐4i‐BP patients who were treated at our hospital for 4 years. Patients selected for this study were those who developed BP after initiation of DPP‐4i and were followed up at least 90 days after DPP‐4i cessation, if information and the relevant parameters were available from the medical records. The patients were divided into two cohorts: a spontaneous remission group and an exacerbation group showing worsening BP or developing infectious IRIS. Serum cytokine/chemokine levels were determined using a multiplex biometric immunoassay.ResultsSerum levels of eotaxin and interferon (IFN)‐α/γ before DPP‐4i cessation were significantly higher in the remission group (161.6 [standard error 21.9] pg/mL and 14.4 [4.8]/9.2 [4.6] pg/mL, respectively) than in the exacerbation group (51.1 [standard error 9.8] pg/mL and 1.6 [1.6]/1.0 [0.5] pg/mL, respectively, p &lt; 0.005). Importantly, regarding changes in cytokine/chemokine levels before and after cessation of DPP‐4i, increasing levels of IFN‐α/γ, interleukin‐10, and interleukin‐1RA following drug cessation were associated with the subsequent development of infectious IRIS.ConclusionsAs observed in patients with coronavirus disease 2019, if the production of IFN‐α/γ and eotaxin occurs early and intense enough before DPP‐4i cessation, virus reactivation as a manifestation of infectious IRIS can be prevented. If not, exuberant virus‐related inflammatory reactions would ensue, as observed in a cytokine storm.

The Eotaxin-1/CCR3 Axis and Matrix Metalloproteinase-9 Are Critical in Anti-NC16A IgE-Induced Bullous Pemphigoid.

Bullous pemphigoid (BP) is the most common autoimmune bullous skin disease of humans and is characterized by eosinophilic inflammation and circulating and tissue-bound IgG and IgE autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. The noncollagenous 16A domain (NC16A) of BP180 has been found to contain major epitopes recognized by autoantibodies in BP. We recently established the pathogenicity of anti-NC16A IgE through passive transfer of patient-derived autoantibodies to double-humanized mice that express the human high-affinity IgE receptor, FcεRI, and human NC16A domain (FcεRI/NC16A). In this model, anti-NC16A IgEs recruit eosinophils to mediate tissue injury and clinical disease in FcεRI/NC16A mice. The objective of this study was to characterize the molecular and cellular events that underlie eosinophil recruitment and eosinophil-dependent tissue injury in anti-NC16A IgE-induced BP. We show that anti-NC16A IgEs significantly increase levels of key eosinophil chemoattractants, eotaxin-1 and eotaxin-2, as well as the proteolytic enzyme matrix metalloproteinase-9 (MMP-9) in the lesional skin of FcεRI/NC16A mice. Importantly, neutralization of eotaxin-1, but not eotaxin-2, and blockade of the main eotaxin receptor, CCR3, drastically reduce anti-NC16A IgE-induced disease activity. We further show that anti-NC16A IgE/NC16A immune complexes induce the release of MMP-9 from eosinophils, and that MMP-9-deficient mice are resistant to anti-NC16A IgE-induced BP. Lastly, we find significantly increased levels of eotaxin-1, eotaxin-2, and MMP-9 in blister fluids of BP patients. Taken together, this study establishes the eotaxin-1/CCR3 axis and MMP-9 as key players in anti-NC16A IgE-induced BP and candidate therapeutic targets for future drug development and testing.