Serum MCP-1 Research Articles

A Balanced Dietary Ratio of n-6:n-3 Polyunsaturated Fatty Acids Exerts an Effect on Total Fatty Acid Profile in RBCs and Inflammatory Markers in Subjects with Obesity.

The n-3 polyunsaturated fatty acids (PUFAs) can reduce inflammatory markers and may therefore be useful in obesity management. The aim of this study was to analyze the effect of supplementation with n-3 PUFAs on total fatty acid profile in red blood cells (RBCs), as well as biochemical and inflammatory markers, in subjects with obesity. The study consisted in a randomized placebo-controlled, double-blind clinical trial involving 41 subjects with obesity during a 4-month follow-up. Individuals were randomly assigned to two groups: n-3 PUFA supplementation (1.5 g fish oil) and placebo (1.5 g sunflower oil). Anthropometric, biochemical, dietetic, cytokine and total fatty acid profiles in RBCs were measured. Both groups increased their PUFA intake and DHA incorporation in RBCs. However, the placebo group showed a reduction in serum IL-8 and MCP-1 at the end of the study. A multiple linear regression model adjusted by body fat mass and sex showed that an increase in DHA in RBCs decreased the serum IL-8 levels in both study groups at the end of the study. Our results highlight the role of dietary DHA and n-3 supplementation usefulness in exerting beneficial anti-inflammatory effects.

The relationship between neuropathic pain and serum endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, VEGF-A levels in fibromyalgia patients and molecular docking results

Purpose: The most important clinical finding of fibromyalgia syndrome (FMS) is pain. Its etiology has not been fully elucidated. This study was planned to determine the relationship between endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-a, VEGF-A levels and pain/neuropathic pain in FMS patients.
 Materials and Methods: Forty-four FMS patients who met the inclusion criteria and 44 age-matched premenopausal healthy controls were recruited. The fibromyalgia group was evaluated in terms of Visual Analog Scale, Beck Depression Scale, Beck Anxiety Scale, Fibromyalgia Impact Questionnaire and LANSS Pain Scale. Serum endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, and VEGF-A values were determined by the ELISA method. Protein-protein interaction was evaluated by molecular docking analysis. Bioinformatics analysis was performed using the STRING v 11.5 protein interaction tool.
 Results: Endocan, ET-1, IL-1, IL-6, IL-8, MCP-1, TNF-α, and VEGF-A were significantly higher in FMS patients than the control group. 24 of 44 patients had neuropathic pain. No correlation was found between pain/neuropathic pain and serum markers levels. High interaction and homology scores of the proteins were defined.
 Conclusion: The pain/neuropathic pain relationship of these markers could not be determined, but the calculated binding energies and activities of the proteins provided important clues for future studies.

Prophylactic consequences of sodium salicylate nanoparticles in cisplatin-mediated hepatotoxicity

Unintended side effects linked to the antineoplastic drug cisplatin are a major drawback in its clinical application. The underlying source of these side effects include the generation of reactive oxygen species which are toxic and damaging to tissues and organs. In the present study the anti-inflammatory and antioxidant potential of sodium salicylate was assessed against cisplatin-induced hepatotoxicity in albino rats. Sodium salicylate was used as a model drug and loading into hollow structured porous silica using ultrasound-assisted sol–gel method to produce a nanoemulsion. Transmission Electron Microscopy and Dynamic Light scattering analysis were employed to assess the structural properties and stability of this model. Liver function was assessed by measuring biomarkers including ALT, AST & GGT and oxidant/antioxidant markers including MDA, NO, PON, GSH, MCP1 & AVP in serum or liver tissue. Additionally, blood leukocyte DNA damage was evaluated. Cisplatin significantly altered the normal levels of all biomarkers confirming its hepatotoxic effects. In contrast, treatment with sodium salicylate-loaded silica nanoemulsion significantly restored the levels of these markers. The finding suggests the protective effects of this model drug in preventing cisplatin-induced hepatotoxicity, and therefore may have implications in attenuating cisplatin-induced hepatotoxicity.

#5187 GREASE II: A PHASE II RANDOMIZED, 24-MONTH, PARALLEL-GROUP, SUPERIORITY STUDY TO EVALUATE THE EFFICACY OF A KETOGENIC DIET IN ADPKD PATIENTS

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is the 4th cause of end-stage renal disease in Western Countries, nevertheless still represents an illness with a significant unmet medical need. In recent years, deregulation in glucose metabolism in ADPKD has been identified. Data suggest that cystic cells shift their energy metabolism from oxidative phosphorylation to aerobic glycolysis. Preclinical experiences show beneficial effects in terms of cystic size reduction, interstitial fibrosis and disease progression, targeting these deregulated metabolic pathways by ketosis induction. A ketogenic diet treatment approach, such as a Modified Atkins Diet (MAD), to ADPKD represents an interesting therapeutic strategy, because of its low cost, tolerability and safety [1]. The Primary Endpoint of this study is the evaluation of the effect of the MAD protocol on the modification of the Total Kidney Volume (TKV), formally qualified, both by FDA and by EMA, as a prognostic enrichment biomarker for selecting patients at high risk for a progressive decline. Method the initial protocol [2] has been modified in a multicentric study that involves the Divisions of Nephrology of AOU Policlinico di Modena (Modena, Italy) and Policlinico di Sant'Orsola (Bologna, Italy). GREASE II is supported by the Italian Ministry of Health (Ricerca Finalizzata grant no. RF-2021-12374522). During the run-in period, 90 patients will follow a Balanced Normocaloric Diet (BND). In the week preceding the randomization, patients will perform a baseline MRI. Patients will be then randomized to MAD or BND according to a stratified 1:1 ratio. Patients will be followed for 12 months at scheduled clinical and dietetic visits. In the 12ve month, the patients on the MAD arm will be switched to BND and a second MRI will be performed after a month (± 7 days). After the MRI, the patients will be switched again to their original MAD. Patients will be followed for further 12 months at scheduled clinical and dietetic visits. At the 24th month, patients of the MAD arm will be switched once again to BND and after a month (± 7 days) a final visit will be performed (Fig. 1). As co-primary endpoint tolerability and safety will be assessed. Furthermore, as secondary outcomes, the study will evaluate renal function decline, total liver volume (TLV) and the impact of the diets on urinary and serum markers β2MG and MCP-1. Results we expect to obtain a reduction of the TKV in the group of patients treated by the MAD protocol. Safety and tolerability are coprimary endpoints of the study. As secondary exploratory outcomes, the study will evaluate the effect of the diet on the TLV and quality of life (ADPKD-IS and SF-12 questionnaires). This clinical trial will allow us to evaluate the proof of concept of the therapeutic efficacy of MAD in the ADPKD clinical setting. Conclusion GREASE II represents the first multicenter RCT evaluating the reduction of the TKV in ADPKD and renal function decline. The identification of a coordinated reduction of TKV and renal function decline in the patients randomized to the MAD compared to the BND will suggest a protective role of the ketogenic diet against disease progression of ADPKD.

Impact of the MCP-1-2518A>G polymorphism on COVID-19 severity in the Iranian population: A case-control study.

As a result of SARS-CoV-2 infection, the host's immune system is disrupted, and chemokines and cytokines are intensified to eliminate the virus, resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19 have been observed to have elevated levels of MCP-1, a chemokine associated with the severity of the disease. In some diseases, polymorphisms in the regulatory region of the MCP-1 gene correspond to serum levels and disease severity. An attempt was made in this study to assess the relationship between MCP-1 G-2518A and serum MCP-1 levels in Iranian COVID-19 patients and the severity of the disease. In this study, patients were randomly sampled from outpatients on the first day of diagnosis and from inpatients on the first day of their hospitalization. Patients were classified into the outpatient (without symptoms or with mild symptoms) and inpatient (with moderate, severe, and critical symptoms) groups. The serum level of MCP-1 was measured by ELISA and the frequency of MCP-1 G-2518A gene polymorphism genotypes in COVID-19 patients was checked by the RFLP-PCR method. Participants with COVID-19 infection had a higher rate of underlying diseases, such as diabetes, high blood pressure, kidney disease, and cardiovascular disease than the control group (P-value<0.001). Also, the frequency of these factors in inpatients was significantly higher compared to outpatients (P-value<0.001). Additionally, the level of MCP-1 in serum was significantly different with an average of 11.90 in comparison to 2.98 in the control group (P-value, 0.05), which is attributed to elevated serum levels among patients in hospitals with an average of 11.72 in comparison to 2.98 in the control group. Compared with outpatients, inpatients had a higher frequency of the G allele of the MCP-1-2518 polymorphism (P-value<0.05), while a notable difference was observed in the serum level of MCP-1 in COVID-19 patients with the MCP-1-2518 AA genotype in the whole group in comparison to the control group (P-value: 0.024). Totally, the results showed that a high frequency of the G allele is related to hospitalization and poor outcome in COVID-19 cases.

Effect of Bifidobacterium bifidum G9-1 on the Intestinal Environment and Diarrhea-Predominant Irritable Bowel Syndrome (IBS-D)-like Symptoms in Patients with Quiescent Crohn's Disease: A Prospective Pilot Study.

Diarrhea-predominant irritable bowel syndrome (IBS-D)-like symptoms are distressing for patients with quiescent Crohn's disease (qCD) and worsen their quality of life. In the present study, we assessed the effect of the probiotic Bifidobacterium bifidum G9-1 (BBG9-1) on the intestinal environment and clinical features in patients with qCD. Eleven patients with qCD, who met the Rome III diagnostic criteria for IBS-D, received BBG9-1 (24 mg) orally three times daily for 4 weeks. Indices of the intestinal environment (fecal calprotectin level and gut microbiome) and clinical features (CD/IBS-related symptoms, quality of life and stool irregularities) were evaluated before and after treatment. Treatment with BBG9-1 tended to reduce the IBS severity index in the studied patients (p = 0.07). Among gastrointestinal symptoms, abdominal pain and dyspepsia tended to be improved by the BBG9-1 treatment (p = 0.07 and p = 0.07, respectively), and IBD-related QOL showed a significant improvement (p = 0.007). With regard to mental status, the patient anxiety score was significantly lower at the endpoint of BBG9-1 treatment than at the baseline (p = 0.03). Although BBG9-1 treatment did not affect the fecal calprotectin level, it suppressed the serum MCP-1 level significantly and increased the abundance of intestinal Bacteroides in the study patients. The probiotic BBG9-1 is able to improve IBD-related QOL with a reduction of anxiety score in patients with quiescent CD and IBS-D-like symptoms.

Role of adiponectin, resistin and monocyte chemo-attractant protein-1 in overweight/obese asthma phenotype in children

BackgroundAsthma is a chronic inflammatory disorder of the airways with diverse overlapping pathologies and phenotypes contributing to a significant heterogeneity in clinical manifestations. Obesity may modify asthma risk, phenotype, and prognosis. A suggested mechanism linking obesity and asthma is through systemic inflammation. Adipokines secreted by adipose tissue were suggested to provide a link between obesity and asthma.ObjectiveTo have an understanding for the contribution of adiponectin, resistin and MCP-1 to development of distinct asthma phenotype in overweight/obese children through assessment of their serum level and correlation to pulmonary function tests.Subjects and methodsThe study included 29 normal weight asthmatics, 23 overweight/obese asthmatic children and 30 controls. All cases were subjected to detailed history taking, thorough examination and pulmonary function tests. Serum adiponectin, resistin, MCP-1 and IgE were assessed to all recruited subjects.ResultsAdiponectin level was significantly higher in overweight/obese asthmatics (24900 ± 1600 ng/ml) compared to normal weight asthmatics (21700 ± 1700 ng/ml) and control (23000 ± 3200 ng/ml), (p < 0.001 & 0.051 respectively). Normal weight asthmatics had significantly lower adiponectin level than control, (p = 0.039). A significant low level of MCP-1 in overweight/obese asthmatics (149.5 (20—545) ng/L) compared to control (175 (28 -1123.5) ng/L), p = 0.037. No significant difference was found regarding resistin. Normal weight asthmatics had significantly lower FEV1% and FVC% compared to overweight/obese asthmatics (p = 0.036, 0.016 respectively). A significant positive correlation was found between (FEV1%, FVC) and BMI in normal weight asthmatics (P = 0.01, < 0.01 respectively) and a significant negative correlation between PEF and BMI (-0.42, p = 0.05) in obese/overweight asthmatics. Resistin/adiponectin ratio was not affected by sex, degree of asthma severity or level of asthma control in either normal weight or overweight/obese asthmatic.ConclusionThis work could suggest that adiponectin may play a role in overweight/obese asthma phenotype where it is possible to have a dual action (pro & anti- inflammatory). It seems that resistin had no role in asthma pathogenesis.

The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts

BackgroundGrowing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. MethodsU-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. ResultsThere were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). ConclusionsThe current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition.

Effects of dapagliflozin on cardiac function indexes and serum MCP-1 levels in patients with Type 2 diabetes mellitus complicated with heart failure

ABSTRACT Type 2 diabetes mellitus (T2DM) and heart failure (HF) are common in clinic, and they often coexist, triggering poor prognosis of patients and increasing hospitalization rates and mortality. Due to some common pathophysiological mechanisms between T2DM and HF, the two have synergistic effects and require collaborative management . In terms of the treatment of T2DM combined with HF, the effects of drugs on both diseases need to be considered to prevent the impact of HF drugs on glycometabolism. As an SGLT2 inhibitor, dapagliflozin can excrete glucose through the kidneys, reduce blood volume, decrease cardiac load to some extent, improve HF symptoms, and better control blood glucose . Therefore, this study selected 60 HF patients complicated with T2DM as the research subjects, and divided them into control group (CLG, conventional medical treatment) and observation group (ONG, dapagliflozin treatment) to explore the effects of dapagliflozin through comparative analysis. According to the results, compared with CLG, ONG had better improvement of blood glucose, cardiac function, and serum levels (P < 0.05), and a lower rehospitalization rate (P < 0.05), with no obvious between-group differences in the incidence of hypotension and emaciation (P > 0.05). These results showed that dapagliflozin in the treatment of T2DM with HF can improve blood glucose levels, cardiac function indexes and inflammatory factor levels, and decrease rehospitalization rates, presenting good clinical efficacy.

Abstract 1842: The safety assessment and the pharmacodynamics evaluation of therapeutic cytokine in non-human primates

Abstract Cytokines are indispensable regulators of innate and adaptive immunity that transfer signals between cells over short distances. Given their abilities to initiate and activate immune responses, cytokines have long been utilized in cancer therapy, whereas there are limitations, short half-life, pleiotropism, functional redundancy, and side effects, slow down the wide application of cytokine therapy. Thus, evaluating the pharmaceutical properties of cytokines or their translated forms, such as supercytokines, immunocytokines, engager cytokines, and synthetic cytokines, in non-human primates shall be a substantial approach to guide and define clinical trial strategies of cytokine-based therapies. In this study, Interleukin-15 (IL-15) is preferably focused due to its potential in proliferating natural killer cells and cytotoxic T lymphocytes by which host’s immunity was boosted to fight against tumor progression. To evaluate the safety and pharmacodynamics of IL-15 in vivo, rhesus macaques were administered intravenously with recombinant human IL-15 (rhIL-15). We revealed that intravenous administration of rhIL-15 to rhesus macaques caused a slightly weight loss and neutropenia, while no other abnormalities were observed during the whole study. Moreover, the level of C-reactive protein (CRP) was found significantly elevated which was consistent with the increased abundance of MCP1, CCL4, and IL-RA chemokines in serum, suggesting that IL-15 treatment induces acute inflammatory response. Furthermore, flow cytometry analysis showed the activation, proliferation and expansion of memory T and NK cells after receiving IL-15. In conclusion, our study deepens the understanding of T and NK cell homeostasis after IL-15 administration in NHPs and may offer critical clinical strategies for human trials. Citation Format: Wei Li, Yixuan Xu, Xin Zhou, Dan Zhu, Meng Xiao, Yulin Zhou, Zhijie Yang, Haodong Li, Bo Pang, Xinghai Song, Yan Xiao, Wenting Shi, Qian Qian, Qingyang Gu. The safety assessment and the pharmacodynamics evaluation of therapeutic cytokine in non-human primates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1842.

Edible O. fragrans flower ameliorates LPS-induced inflammatory responses through suppressing NF-κB and AP-1 pathways

Osmanthus fragrans (Thunb.) Lour. is one of the most common edible plants in China. Its flower (O. fragrans flower) is widely utilized as a food ingredient and traditional Chinese medicine for hundreds of years. In lipopolysaccharide (LPS)-activated macrophages, OFE suppressed the pro-inflammatory mediators (iNOS, MCP-1, IL-6 and IL-1β) at the transcriptional and translational levels, showing a potent anti-inflammatory effect. Mechanism study indicated that, OFE inhibited IκBα phosphorylation and prevented the nuclear translocation of p65, thereby inactivating nuclear factor-κB (NF-κB) signaling. Concurrently, OFE also suppressed AP-1 signaling through inhibiting the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38 MAPK. In endotoxemia mice, a single intraperitoneal administration of OFE significantly decreased serum IL-6 and MCP-1 levels. Our study demonstrates that O. fragrans flower may be the beneficial food for inflammatory diseases.

Cornelian Cherry (Cornus mas L.) Iridoid and Anthocyanin-Rich Extract Reduces Various Oxidation, Inflammation, and Adhesion Markers in a Cholesterol-Rich Diet Rabbit Model.

Atherogenesis leads to the development of atherosclerosis, a progressive chronic disease characterized by subendothelial lipoprotein retention and endothelial impairment in the arterial wall. It develops mainly as a result of inflammation and also many other complex processes, which arise from, among others, oxidation and adhesion. Cornelian cherry (Cornus mas L.) fruits are abundant in iridoids and anthocyanins-compounds with potent antioxidant and anti-inflammatory activity. This study aimed to determine the effect of two different doses (10 mg and 50 mg per kg of body weight, respectively) of iridoid and anthocyanin-rich resin-purified Cornelian cherry extract on the markers that are important in the progress of inflammation, cell proliferation and adhesion, immune system cell infiltration, and atherosclerotic lesion development in a cholesterol-rich diet rabbit model. We used biobank blood and liver samples that were collected during the previous original experiment. We assessed the mRNA expression of MMP-1, MMP-9, IL-6, NOX, and VCAM-1 in the aorta, and the serum levels of VCAM-1, ICAM-1, CRP, PON-1, MCP-1, and PCT. The application of the Cornelian cherry extract at a dose of 50 mg/kg bw resulted in a significant reduction in MMP-1, IL-6, and NOX mRNA expression in the aorta and a decrease in VCAM-1, ICAM-1, PON-1, and PCT serum levels. The administration of a 10 mg/kg bw dose caused a significant decrease in serum ICAM-1, PON-1, and MCP-1. The results indicate the potential usefulness of the Cornelian cherry extract in the prevention or treatment of atherogenesis-related cardiovascular diseases, such as atherosclerosis or metabolic syndrome.

Evaluation of Biomarkers from Peritoneal Fluid as Predictors of Severity for Abdominal Sepsis Patients Following Emergency Laparotomy.

Intra-abdominal infection is considered the second most common cause of sepsis and results in localized or diffused inflammation of the peritoneum. The main treatment for abdominal sepsis is an emergency laparotomy for source control. However, surgical trauma also causes inflammation, and patients become susceptible to postoperative complications. Therefore, it is necessary to identify biomarkers that can be used to distinguish sepsis from abdominal infection. This prospective study investigated whether cytokine levels in the peritoneum could predict complications and indicate severity of sepsis following emergency laparotomy. We prospectively observed 97 patients with abdominal infection admitted to the Intensive Care Unit (ICU). After emergency laparotomy,SEPSIS-3 criteria were used for the diagnosis of sepsis or septic shock. Blood and peritoneal fluid samples were drawn at postoperative admission to the ICU and cytokine concentrations were measured by flow cytometry. Fifty-eight postoperative patients were enrolled. We found significant elevations in the peritoneal concentrations of IL-1β, IL-6, TNF-α, IL-17, and IL-2 in patients with sepsis or septic shock compared to the patients without sepsis after surgery. Positive correlations between levels of these peritoneal cytokines with APACHE II scores were found: IL-6, in particular, had the highest correlation coefficient of 0.833. Meanwhile, IL-10 in blood, MCP-1 and IL-8 in both blood and peritoneum were simultaneously increased in patients with sepsis and septic shock, and also positively correlated with disease severity. The cytokine storm that occurs in the abdominal cavity after emergency laparotomy may be the main mechanism leading to sepsis. It may be valuable to measure IL-1β, IL-6, TNF-α,IL-17, IL-2, MCP-1, and IL-8 in the peritoneal fluid, combined with serum IL-10, MCP-1 and IL-8, in a panel of cytokines, to assess the severity of sepsis and predict mortality from abdominal infection after emergency laparotomy.

Expression profile of cytokines and chemokines in a mouse high-altitude cerebral edema model.

High-altitude cerebral edema (HACE) is considered to be the end-stage of acute mountain sickness (AMS); however, its pathophysiological mechanism remains unknown. Increasing evidences support that inflammation is an important risk factor for the occurrence of HACE. Including our published papers, previous studies demonstrated that the levels of IL-6, IL-1β, and TNF-α in both serum and hippocampus were increased in the mouse HACE model induced by LPS stimulation combined with hypobaric hypoxia exposure; however, the expression profile of other cytokines and chemokines remains unknown. This study was to analyze the expression profile of cytokines and chemokines in the HACE model. The mouse HACE model was established by LPS stimulation combined with hypobaric hypoxia exposure (LH). The mice were divided into the normoxic group, LH-6h group, LH-1d group, and LH-7d group. Brain water content (BWC) was determined using the wet/dry weight ratio. The levels of 30 cytokines and chemokines in the serum and hippocampal tissue were detected using LiquiChip. The mRNA expression of cytokines and chemokines in hippocampal tissue were determined by q-PCR. In the current study, we found that the brain water content was increased after the combinational treatment of LPS and hypobaric hypoxia. The results of LiquiChip showed that, in the serum and hippocampal tissue, most factors in all 30 cytokines and chemokines were dramatically upregulated at 6h, and then declined at the 1std and 7thd. Among these factors, G-CSF, M-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β were all increased in both serum and hippocampal tissue at 6h. In addition, the results of q-PCR showed the mRNA levels of G-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β in hippocampal tissue were dramatically upregulated at 6h. This study showed that the dynamic expression profile of 30 cytokines and chemokines in a mouse HACE model induced by LPS plus hypobaric hypoxia. The levels of G-CSF, MCP-1, KC, MIG, Eotaxin, Rantes, IP10, IL-6, MIP-2, and MIP-1β in both serum and hippocampus were significantly increased at 6h, which may be involved in the occurrence and development of HACE.

A Prospective Study of Mid-Trimester MCP-1 Levels as a Predictor of Preterm Delivery.

Background: The prevention of preterm delivery (PTD) represents one of the major topics in modern obstetrics. The aim was to design a prospective study and investigate if mid-trimester serum and amniotic fluid levels of MCP-1 could predict the occurence of spontaneous PTD. Methods: The study involved 198 women who underwent genetic amniocentesis and blood sampling in the middle of their trimester. After applying the criteria for inclusion in the study, there were 16 respondents in the study group, and 38 respondents in the control group. Level of MCP-1 in amniotic fluid and serum was measured with commercially available enzyme-linked immunosorbent assays (ELISA) and statistical analysis was conducted. Results:&amp;nbsp;There was no statistically significant difference in serum or amniotic fluid MCP1 levels between PTD and the control groups. Conclusion: The results suggest that MCP-1 is probably not the most relevant marker for predicting PTD. This study provides new normative data for MCP-1 levels in amniotic fluid and maternal sera and is a valuable tool for future diagnostic and comparative studies.

Evaluation of 34 Cytokines and Vitamin D Status Reveal A Sexually-Dimorphic Active Immune Response to SARS-CoV-2.

Several observational studies have inconsistently demonstrated that vitamin D deficiency is a risk factor for coronavirus disease-19 (COVID-19) infection and severity. Discrepancies in results may partially be explained by the individuals' immune profiles, which are modulated, in varying degrees, by vitamin D status and sex hormones. In this study we evaluated the differences and associations of serum levels of 25(OH)D with 34 cytokines in 220 adults (82 controls (41 males; 41 females) and 138 SARS-CoV-2 patients (79 males and 59 females)) with and without COVID-19. Serum 25(OH)D levels were significantly lower in the SARS-CoV-2 group than in the controls. Serum IP-10, MCP-1, CRP, IFNγ, IL-10, IL-13, IL-17α, IL-23, and IL-6 were significantly higher in COVID-19 patients compared to controls. Serum levels of VEGF, IFNγ, IL-13, and IL-5 were significantly higher in male patients than in females. 25(OH)D was significantly correlated with EFG (R = 0.39, p &lt; 0.05) and IL-15 (R = 0.39, p &lt; 0.05) in male patients, while it was inversely correlated with CRP (R = -0.51, p &lt; 0.05) in female patients. Altered levels of cytokines, chemokines, and vitamin D were observed in SARS-CoV-2 adult patients. These expressions were sexually dimorphic and thus highlight the sex-specific nature of the active immune response following SARS-CoV-2 infection.

RCsHscB Derived from Clonorchis sinensis: A Carcinogenic Liver Fluke Ameliorates LPS-Induced Acute Hepatic Injury by Repression of Inflammation.

Sepsis-associated acute liver injury caused by spillovers of bacteria and endotoxins (lipopolysaccharide, LPS) into the liver remains a public health issue due to the lack of specific therapeutic approaches. Previous studies showed that the recombinant protein HscB (rCsHscB) of Clonorchis sinensis, a carcinogenic liver fluke, had an anti-inflammatory effect and could alleviate inflammatory diseases such as enteritis; however, whether it can prevent sepsis-associated acute liver injury induced by LPS is still unknown. In our current study, the therapeutic effects and the potential mechanisms of rCsHscB on LPS-induced acute liver injury were investigated both in vivo and in vitro. The data showed that rCsHscB prevented LPS-induced liver damage, as demonstrated by histopathological observation and hepatic damage markers (the activities of serum ALT and AST) in a murine model of sepsis-associated acute liver injury. rCsHscB also significantly reversed the high levels of serum IL-6 and MCP-1 induced by LPS. In addition, rCsHscB attenuated the production of LPS-induced proinflammatory cytokines, including IL-6 and TNF-α, in a macrophage cell line-RAW264.7, through possible mediation by the MAPK signaling pathway in vitro. In conclusion, the present study demonstrates that rCsHscB derived from a fluke C. sinensis protects against sepsis-associated acute liver injury induced by LPS, which may be attributed to the inhibition of the MAPK signaling pathway. Our present study provides a potential therapeutic strategy for sepsis-associated acute liver injury.

The association of γδT lymphocytes with cystic leukomalacia in premature infants.

Periventricular leukomalacia (PVL) is an essential cause of cerebral palsy in preterm infants, and cystic PVL (cPVL) is the most severe form of the disease. The pathogenesis of cPVL is complex, and immune imbalances and inflammatory responses may play an essential role in it. This study aimed to investigate the correlation between peripheral blood lymphocyte subsets, especially γδT cells with the pathogenesis of cPVL in preterm infants. Peripheral blood from preterm infants with GA < 32 weeks and BW < 1,500 g was used in this study and was collected at 34 weeks corrected gestational age and within 24 h after the diagnosis with cranial MRI or cranial ultrasound. The infants were divided into cPVL groups and control groups. Flow cytometry was used to detect peripheral blood γδT, CD3+, CD4+, CD8+, and the proportion of total lymphocytes. Multiplex cell assays were used to detect the concentration of extracellular serum cytokines IL-6, IL-2, IL-8, IL-17A, IL-10, IL-1RA, eotaxin (CCL11), MCP-1 (CCL2), CXCL1, G-CSF, and IFNγ. A follow-up visit was carried out when the patient was 3 years old. After correcting for confounding factors, the proportion of peripheral blood γδT in the cPVL group was significantly lower than that in the control group (β: 0.216; 95% CI: 0.058-0.800, P < 0.022). Peripheral blood γδT (AUC: 0.722, P=0.006) and multivariate binary regression model (AUC: 0.865, P < 0.000) have good diagnostic values for cPVL. Peripheral blood γδT has some predictive power for neurodevelopmental outcomes in preterm infants (AUC: 0.743, P = 0.002). It seems that peripheral blood γδT cells are inversely correlated with cPVL, which is not only a risk factor for cPVL disease but also neurodevelopmental outcomes in preterm infants. However, the causality of cPVL and various lymphocytes is unclear and needs further study.

Evaluation of IL-10, MCP-1, IFN gamma, and protectin D1 levels in patients with Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is one of the most prevalent autoimmune endocrine diseases and caused by the loss of immune tolerance for the thyroid gland. Many pathophysiological mechanisms were speculated about the development of HT. In our study, we aimed to reveal the relationship between HT and IL-10, MCP-1, IFNɤ, and PD1 levels and compare them with control subjects. We collected 37 patients with HT and 25 controls referred to our outpatient clinic. The diagnosis of HT was based on the detection of circulating antibodies to thyroid antigens and decreasing echogenicity on thyroid USG in patients with appropriate clinical characteristics. Serum IL-10, MCP-1, IFNɤ, and PD1 levels were detected using an ELISA KIT (96T) method according to the manufacturer's instructions. All subjects were euthyroid (median TSH level was 1.68mU/L in HT vs 1.83mU/L in the controls, p = 0.672). Twenty-three of 37 patients with HT were taking L-thyroxin replacement. Levels of serum IL-10, IFNɤ, and PD1 in patients with HT were higher than the controls, but the differences were not statistically significant (p = 0.393, p = 0.495, and p = 0.052 respectively). The serum levels of MCP-1 in HT patients were statistically different and higher than the controls (p = 0.018). Correlation analysis displayed significant associations between IL-10, MCP-1, IFNɤ, and PD1 levels. Our study demonstrated that serum MCP-1 levels in HT patients were significantly increased; on the other hand, significant difference was not found between HT patients and the controls in terms of serum IL-10, IFNɤ, and PD1 levels.

Lentiviral Gene Transfer Corrects Immune Abnormalities in XIAP Deficiency

BackgroundX-linked inhibitor of apoptosis protein (XIAP) deficiency is a severe immunodeficiency with clinical features including hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD) due to defective NOD2 responses. Management includes immunomodulatory therapies and hematopoietic stem cell transplant (HSCT). However, this cohort is particularly susceptible to the chemotherapeutic regimens and acutely affected by graft-vs-host disease (GvHD), driving poor long-term survival in transplanted patients. Autologous HSC gene therapy could offer an alternative treatment option and would abrogate the risks of alloreactivity.MethodsHematopoietic progenitor (Lin−ve) cells from XIAPy/− mice were transduced with a lentiviral vector encoding human XIAP cDNA before transplantation into irradiated XIAP y/− recipients. After 12 weeks animals were challenged with the dectin-1 ligand curdlan and recovery of innate immune function was evaluated though analysis of inflammatory cytokines, body weight, and splenomegaly. XIAP patient-derived CD14+ monocytes were transduced with the same vector and functional recovery was demonstrated using in vitro L18-MDP/NOD2 assays.ResultsIn treated XIAPy/− mice, ~40% engraftment of gene-corrected Lin−ve cells led to significant recovery of weight loss, splenomegaly, and inflammatory cytokine responses to curdlan, comparable to wild-type mice. Serum IL-6, IL-10, MCP-1, and TNF were significantly reduced 2-h post-curdlan administration in non-corrected XIAPy/− mice compared to wild-type and gene-corrected animals. Appropriate reduction of inflammatory responses was observed in gene-corrected mice, whereas non-corrected mice developed an inflammatory profile 9 days post-curdlan challenge. In gene-corrected patient CD14+ monocytes, TNF responses were restored following NOD2 activation with L18-MDP.ConclusionGene correction of HSCs recovers XIAP-dependent immune defects and could offer a treatment option for patients with XIAP deficiency.