Lower Serum Levels Of IL-6 Research Articles

The Effects of Convalescent Plasma Transfusion on Serum Levels of Macrophage-Associated Inflammatory Biomarkers in Patients with Severe COVID-19.

As an antibody-based therapy, plasma therapy has been used as an emergency therapeutic strategy against severe acute respiratory syndrome coronavirus type 2 infection. Due to the critical role of macrophages in coronavirus disease-19 (COVID-19)-associated hyperinflammation, the main objective of this study was to assess the effect of plasma transfusion on the expression levels of the inflammatory biomarkers involved in activation and pulmonary infiltration of macrophages. The target population included 50 severe hospitalized COVID-19 patients who were randomly assigned into 2 groups, including intervention and control. Serum levels of chemokine (C-C motif) ligand (CCL)-2, CCL-3, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. Moreover, quantitative real-time polymerase chain reaction (PCR) was carried out to assess the relative expression of nuclear factor (NF)-κB1, NF-κB2, nuclear factor erythroid 2 p45-related factor 2 (NRF-2), and thioredoxin-interacting protein genes. Sampling was done at baseline and 72 h after receiving plasma. The intervention group demonstrated significantly lower serum levels of IL-6, TNF-α, and CCL-3. In addition, real-time PCR data analyses showed that the relative expression of NF-κB2 was significantly declined in the patients who received plasma. The use of convalescent plasma probably has a significant inhibitory effect on the cytokines, chemokines, and inflammatory genes related to macrophage activation, which are closely associated with the worsening of clinical outcomes in severe COVID-19.

Elevated interleukin (IL)-6 as a predictor of disease severity among Covid-19 patients: a prospective cohort study

Backgroundaccompanied to the spreading of coronavirus disease 2019 (Covid-19) in the world, identifying factors related to the severity of the disease is one of the interests of physician and medical researchers. We hypothesized that interleukin 6 serum level is associated with severe outcome.MethodsIn this longitudinal prospective cohort study we enrolled 208 confirmed COVID-19 patients who were admitted to the Tohid Hospital (Sanandaj, Iran). Patients were classified into two groups based on IL-6 value in the first day of admission, elevated (n = 107) or not elevated/normal (n = 101), and followed until the occurrence of final outcome (death or discharge from the hospital). Data were analyzed using univariate methods, Chi-squared and independent two sample T test. The relationship between the independent variables and our interesting outcomes were investigated by multiple linear and penalized logistic regression modeling.ResultsA total of 208 patients, 51% female and mean age 53.6 ± 16.3 years, including 107 elevated and 101 non-elevated IL-6 patients, were followed. No significant difference was observed between the two groups in demographic and clinical characteristics. Although not significant, logistic regression results showed that the chance of death occurrence among patients with elevated IL-6 are 3.91 times higher. According to the multiple linear regression modeling, elevated IL-6 significantly increased the duration of hospital stay (P = 0.02). Frequency of ICU admission (P = 0.04) and mean of ICU stay (P = 0.8) are also higher in elevated IL-6 group.ConclusionThis study revealed that elevated IL-6 is significantly related to prolongation of hospital stay in Covid-19 patients. Although not significant, the occurrence of death among patients who had increased IL-6 in the time of admission was higher than patients with normal or lower serum levels of IL-6.

Benzoylpaeoniflorin Activates Anti-Inflammatory Mechanisms to Mitigate Sepsis in Cell-Culture and Mouse Sepsis Models.

Xuebijing injection (XBJI) (comprising of five herbs) is a widely used traditional Chinese medicine for sepsis treatment. However, the bioactive components of XBJI and the mechanisms responsible for its sepsis-mitigating action have not been experimentally determined. One of the main bioactive compounds in XBJI-benzoylpaeoniflorin (BPF)-inhibits the expressions of key mediators of inflammation such as nuclear factor kappa B (NF-κB), cyclooxygenase-1 (COX-1), and COX-2. However, its effects on sepsis have not been determined yet. Therefore, here, we investigated the immunomodulatory effect of BPF on severely inflamed endothelial cells, THP-1 macrophages, peritoneal macrophages, and mice. Human umbilical vein endothelial cells (HUVECs) and THP-1-macrophages were activated using lipopolysaccharide (LPS) after pretreatment with BPF. Subsequently, changes in the expression profiles of pro-inflammatory molecules including inducible nitric oxide synthase (iNOS), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 were determined using quantitative real-time polymerase chain reaction (qPCR) and Western blot analysis. Furthermore, we monitored the phosphorylation of NF-kB and mitogen-activated protein kinases (MAPKs) to determine their activation levels. Using the LPS-induced mouse model of sepsis, we studied the effects of BPF on inflammatory cytokine production, pulmonary histopathology, and survival rates. Finally, we evaluated whether BPF protects against cecal ligation and puncture (CLP)-induced sepsis, as it closely mimics human sepsis. BPF pretreatment inhibited LPS-induced increase in mRNA and protein levels of iNOS, TNF-α, and IL-6 in HUVECs and THP-1-macrophages. It also suppressed LPS-mediated phosphorylation of p65, p38, JNK, and ERK. Mice with LPS-induced-sepsis who were treated with BPF had lower serum levels of IL-6, TNF-α, IL-1β, CXCL1, and CXCL2 than the control mice treated with BPF. Histopathology revealed that BPF treatment alleviated LPS-induced lung damage. In addition, in mice given a lethal dose of LPS, BPF treatment showed a dose-dependent improvement in survival rates. BPF treatment dose-dependently inhibited the LPS-induced IL-6, TNF-α, and CXCL1 production in peritoneal macrophages. BPF treatment also dose-dependently improved the survival rates in mice with CLP-induced sepsis. These results show that BPF alleviates LPS-stimulated septic conditions and protects mice from CLP-induced sepsis. Our research marks BPF as a potential drug in the treatment of sepsis and various inflammatory diseases.

Serum cytokine levels for predicting immune-related adverse events and the clinical response in lung cancer treated with immunotherapy.

BackgroundAt present, immunotherapy has become an important treatment for lung cancer. With the widespread use of immune checkpoint inhibitors (ICIs), we must be strict with the emergence of immune related adverse events (irAEs). There are also some patients who do not respond to immunotherapy. However, there was no biomarkers to predict the safety and efficacy of immunotherapy. The selection of immunotherapy beneficiaries contributes to improving the efficacy and safety of lung cancer treatment.MethodThe electronic medical records of 221 lung cancer patients with complete clinical data who received immunotherapy from the First Affiliated Hospital of Xi ‘an Jiaotong University from November 2020 to October 2021 were collected and followed up. IBM SPSS Statistic 26.0 and R 4.1.2 software were used for statistical analysis and mapping.Results1. A total of 221 lung cancer patients receiving immunotherapy were included in the study. Higher baseline levels of IL-1β (7.88 vs 16.16pg/mL, P=0.041) and IL-2 (1.28 vs 2.48pg/mL, P=0.001) were significantly associated with irAEs. Higher levels of IL-5 (2.64 vs 5.68pg/mL, P=0.013), IFN-α (1.70 vs 3.56pg/mL, P=0.004) and IFN-γ (6.14 vs 21.31pg/mL, P=0.022) after the first cycle therapy were associated with irAEs. There was no statistical significance between cytokines and irAEs after the second cycle therapy. Higher IL-5 levels in peripheral blood (9.50 vs 3.57pg/mL, P=0.032) were associated with the occurrence of irAEs after the third cycle therapy. 2.The efficacy of immunotherapy was assessed in 142 lung cancer patients. There was no statistical significance between baseline cytokine levels and clinical benefit. After the first cycle therapy, the level of serum cytokines had no statistical significance with the occurrence of immunotherapy clinical benefit. Lower serum levels of IL-10 (2.66 vs 1.26pg/mL, P=0.016) and IL-17 (8.47 vs 2.81pg/mL, P=0.015) were associated with clinical benefit after the second cycle therapy. Lower serum levels of IL-6 (10.19 vs 41.07pg/mL, P=0.013) and IL-8 (8.01 vs 17.22pg/mL, P=0.039) were associated with clinical benefit of immunotherapy after the third cycle therapy.Conclusion1. Baseline IL-1β and IL-2 levels in peripheral blood were associated with the occurrence of irAEs in lung cancer patients. The levels of IL-5, IFN-α and IFN-γ during treatment were associated with irAEs. 2. Baseline cytokine levels in peripheral blood were not associated with immunotherapy efficacy. The levels of IL-6, IL-8, IL-10, and IL-17 levels during treatment were associated with immunotherapy efficacy.

Effect of a combination of Xuebijing and thymosin α1 on patients with severe pneumonia complicated with sepsis, and its influence on serum inflammatory factors

Purpose: To investigate the influence of a combination of Xuebijing and thymosin α1 on acute and septic bronchopneumonia (ASB) patients, and the effect of the treatment on inflammation.
 Methods: Eighty-one (81) ASB patients admitted to Tianjin Medical University General Hospital, Tianjin China from January 2015 to July 2019 were enrolled in the study. The patients were assigned to control group (n = 41) and a study group (n = 40). The control patients were treated with Xuebijing injection, i.v., while the study group received a combination of Xuebijing injection and thymosin α1 via the subcutaneous route. Patients’ body temperature, heartbeat, white blood cell count, as well as other parameters, including blood gas indices, serum concentrations of IL-6, TNF-α and C-reactive protein (CRP), as well as well as blood gas indices were determined by enzyme-linked immunosorbent assay (ELISA). Bacterial clearance and therapeutic effectiveness were evaluated pre- and post-treatment.
 Results: Post-therapy basal temperature, breathing, heartbeat, number of white blood cells and other indices decreased in study patients, relative to control (p < 0.05). Moreover, the levels of hydrogen ion concentration (pH) and arterial carbon dioxide partial pressure (PaCO2) were significantly lower in study group than in control group (p < 0.05). Patients in the study group had lower serum levels of IL-6, TNF-α and CRP, when compared to control group, while bacterial load was significantly reduced in study subjects, relative to controls (p < 0.05).
 Conclusion: Combined use of thymosin α1 and Xuebijing is significantly effective in the management of patients suffering from ASB. The combination therapy also improves the hemorheological status of patients. Thus, it is a potential therapeutic strategy for ASB.
 Keywords: Acute bronchopneumonia; Xuebijing; Thymosin α1; Septicemia; Inflammation

Functional Outcome and Inflammatory Response of Patients with Extra-Articular Distal Humeral Fractures following Implantation of Anatomically Precontoured Locking Compression Plates through a Posterior Approach.

Distal humeral fractures are challenging injuries to surgically correct and account for up to 2% of all adult fractures. Surgical management of extra-articular distal humeral fractures is challenging considering surgical approach, implant selection, and position of the implant owing to the availability of different precontoured implants and plate configurations. Anatomically precontoured locking compression plates (APLCPs) allow the placement of angular stable screws right underneath the reduced joint surface fragments. To date, there is a lack of evidence supporting its superiority to conventional locking plate osteosynthesis (LPO) in treating extra-articular distal humeral fractures. The objective of the study is to evaluate the efficacy and safety of APLCPs in the treatment of extra-articular distal humeral fractures. A total of 100 patients diagnosed with humeral fractures and receiving treatments in our hospital between May 2018 and May 2020 fulfilled inclusion and exclusion criteria and were randomly assigned to LPO and APLCP groups according to the odd-even of the order of hospital admission, 50 cases per groups. Clinical endpoints were assessed including operation time; in-bed time; length of hospital stay; volume of intraoperative blood loss; VSA scores before and 24, 48, and 72 h after surgery; MEPS scores before and 3, 6, and 12 months after surgery; range of motion, flexion, and extension of the elbow; serum levels of CK, CRP, and IL-6; and incidence of complications after surgery. It was found that the APLCP group exhibited shortened operation time and in-bed time, decreased length of hospital stay, and reduced volume of intraoperative blood loss compared to the LPO group (all P < 0.001). The two groups had declined VSA scores concomitant with increased MEPS scores after surgery in a time-dependent manner (P < 0.001). Notably, the VSA scores in the APLCP group were all lower than those in the LPO group at indicated time points (24, 48, and 72 h) after surgery (P < 0.001). Besides, the MEPS scores in the APLCP group were all higher than those in the LPO group at indicated time points (3, 6, and 12 months) after surgery (P < 0.001). It was revealed that the patients receiving extra-articular distal humeral APLCP through posterior approaches exhibited greater ranges of motion, flexion, and extension of the elbow than those receiving LPO after surgery (P < 0.001). The patients receiving extra-articular distal humeral APLCP through posterior approaches exhibited lower serum levels of IL-6, CRP, and CK than those receiving LPO after surgery (IL-6: P=0.007, CRP: P=0.001, CK: P=0.001). The APLCP had a lower total incidence rate of complication than the LPO group (48.00% vs. 18.00%, P=0.003). In conclusion, these data support the notion that the implantation of anatomically precontoured APLCP through a posterior approach allows for improved functional outcomes and attenuated inflammatory response and prevents the incidence of postoperative complications compared to conventional LPO for internal fixation of extra-articular distal humeral fractures.

1014 The influence of cigarette, electronic cigarette and dual use exposure on maternal immune profiles

Although maternal tobacco use is known to alter serum cytokine concentrations, no data exist regarding the influence electronic cigarettes (e-cigs) exposure on the maternal immune profile. The purpose of this study was to describe differences in the cytokine profiles of pregnant e-cig users compared to conventional cigarette smokers and non-smokers. Between 2007 and 2019, a multi-site, prospective cohort study of women with validated tobacco use enrolled participants and controls up to 26 weeks gestation. Serum cytokines (Interleukin (IL)-1β, IL-2, IL-6, IL-8, IL-10, TNFα) CRP, and MMP-8 were measured using a multiplex electrochemiluminescent plate assay during the second trimester (mean gestational age = 22.5 weeks, SD = 1.9). Cytokine levels were log transformed prior to analysis. Analysis of Covariance assessed differences by tobacco use group, adjusting for age and BMI. Post-hoc comparisons were accomplished using Fisher’s Least Significant Differences (LSD) method. All analysis was conducted using SAS v 9.4, with an alpha of .05. 387 participants were enrolled and stratified into conventional cigarettes only (n=132), e-cig only (n=26), conventional + e-cig (dual) (n=96), and nonsmoker (n=133) groups. Adjusting for age and BMI, all tobacco use groups had significantly lower serum levels of IL-6, IL-8, IL-10, CRP, and TNFα concentrations compared to nonsmokers. Conventional only users also had significantly higher levels of IL-1b and IL-10 compared to dual and e-cig only users, and significantly higher CRP compared to dual users. In the e-cig only group, non-significant differences in cytokine profiles were noted compared to dual users. Significant differences were observed in multiple serum cytokines between pregnant cigarette and e-cig users versus non-smokers suggesting a causal association between these exposures and an impaired maternal immune profile. E-cig exposure resulted in a unique profile of cytokines compared to conventional users, which may improve clinical outcomes and requires further study.

Relationship between disease severity and serum IL-6 levels in COVID-19 anosmia

BackgroundAn association between IL-6 levels and cytokine storm syndrome in COVID-19 patients has been suggested. Cases with higher IL-6 levels have more rapid progression and a higher complication rate. On the other hand, COVID-19 cases with anosmia have a milder course of the disease. ObjectiveWe aimed to investigate whether there is a relationship between serum IL-6 levels and presence of anosmia in COVID-19 patients. MethodsPatients with a confirmed diagnosis of COVID-19 based on laboratory (PCR) were stratified into two groups based on presence of olfactory dysfunction (OD). In all cases with and without anosmia; psychophysical test (Sniffin' Sticks test) and a survey on olfactory symptoms were obtained. Threshold (t) – discrimination (d) – identification (i), and total (TDI) scores reflecting olfactory function were calculated. Clinical symptoms, serum IL-6 levels, other laboratory parameters, and chest computed tomography (CT) findings were recorded. ResultsA total of 59 patients were included, comprising 23 patients with anosmia and 36 patients without OD based on TDI scores. Patients with anosmia (41.39 ± 15.04) were significantly younger compared to cases without anosmia (52.19 ± 18.50). There was no significant difference between the groups in terms of comorbidities, smoking history, and symptoms including nasal congestion and rhinorrhea. Although serum IL-6 levels of all patients were above normal values (7 pg/mL), patients with anosmia had significantly lower serum IL-6 levels (16.72 ± 14.28 pg/mL) compared to patients without OD (60.95 ± 89.33 pg/mL) (p = 0.026). ConclusionPatients with COVID-19 related anosmia tend to have significantly lower serum levels of IL-6 compared to patients without OD, and the lower IL-6 levels is related to milder course of the disease. With the effect of low cytokine storm and IL-6 level, it may be said that anosmic cases have a milder disease in COVID-19.

Peptides derived from fermented soybean meal suppresses intestinal inflammation and enhances epithelial barrier function in piglets

ABSTRACT This study was to investigate the effects of peptides derived from fermented soybean meal (FSP) on intestinal inflammation and epithelial barrier function of the piglets. Compared to fed soybean meal, piglets fed with fermented soybean meal (FSBM) exhibit lower serum levels of IL-6, IL-1β and D-lactate, and reduced ileum macrophage infiltration. Besides, the FSBM up-regulated (p < 0.05) expression of mucins and tight junction (TJ) proteins in the jejunum and ileum of piglets. The FSP were prepared with alkali extraction and a 3-kDa molecular weight cut-off membrane system. In vitro, FSP reducing the mRNA expression of IL-6, IL-1β, IL-8 and attenuated Escherichia coli K88-induced inflammation in the intestinal porcine epithelial cells-J2 (IPEC-J2). Furthermore, FSP increased (p < 0.05) the expression of TJ proteins and transepithelial electrical resistance in IPEC-J2 cells. These results suggest that FSP could improve small intestinal health by enhancing epithelial barrier function and suppressing inflammation.

Aquaporin 4 deficiency alleviates experimental colitis in mice.

Aquaporin (AQP) 4 is expressed in the basolateral membrane of colonic epithelial cells, and the purpose of this study was to explore the mechanistic role of AQP4 in experimental colitis. Experimental colitis was induced in AQP4 knockout (AQP4-/-) CD-1 mice and AQP4 wild-type (AQP4wt) mice by oral administration of dextran sulfate sodium (DSS). Experimental colitis was clinically established. Compared with AQP4wt mice, AQP4-/- mice showed increased tolerance to DSS-induced experimental colitis, including lesser degree of weight loss, diarrhea and bleeding, lower disease activity index scores, longer colon lengths, and lesser histologic scores. DSS-treated AQP4-/- mice had lower serum levels of IL-6 and TNF, higher IL-10 level, and lesser inflammatory cell infiltration. DSS-treated AQP4-/- mice also had lower immunostaining of NF-κB p65 as well as nuclear levels of p65 and phosphorylated p65. Sequencing of 16S rRNA indicated that DSS-treated AQP4-/- mice maintained intestinal microbial diversity and had higher Firmicutes/Bacteroidetes ratios and greater relative abundance of Erysipelotrichaceae species. These results suggested for the first time that AQP4 deficiency alleviates experimental colitis in mice. Our study helps to understand the pathogenesis of inflammatory bowel diseases, and blocking AQP4 may represent a novel therapeutic approach for ulcerative colitis.-Wang, L., Tang, H., Wang, C., Hu, Y., Wang, S., Shen, L. Aquaporin 4 deficiency alleviates experimental colitis in mice.

Effects of neuroserpin on clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke

Objective: Neuroserpin (NSP) is known for its neuroprotective effects. The aim of this study was to investigate the relationship between NSP level and clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke.Methods: A total of 133 patients with acute cerebral infarction (ischemia group) and 44 controls were recruited. The modified Rankin Scale (mRS) was used to determine the functional outcome three months after onset. We investigated the relationship between serum NSP levels [on admission and a decrease in NSP levels (10 days after admission versus on admission)] and serum levels of several inflammatory markers.Results: We confirmed that NSP levels on admission in the ischemia group were significantly higher than those in the control group. NSP levels in patients with good outcomes were significantly higher than those in patients with poor outcomes. NSP levels on admission were associated with having a good outcome in these patients. We found that a larger decrease in NSP levels (on admission vs. 10 days after admission) was correlated with lower serum levels of IL-6, IL-1β, and ICAM-1 10 days after admission.Conclusions: A larger decrease in NSP levels related to lower levels of inflammatory marker, while higher NSP levels were associated with lower inflammatory markers and better functional outcomes. Decreasing the infarct size may play a role in this process. These results provide more evidence of the neuroprotective effect of NSP in cerebral ischemic patients. Decrease in the Serum NSP level and NSP level at admission may be considered as potential predictive factors for outcome of acute ischemic stroke.

Aborted myocardial infarction in patients undergoing primary percutaneous coronary intervention

Introduction. The outcome of patients with ST-elevation myocardial infarction (STEMI) strongly depends on a successful reperfusion. In some patients receiving an effective treatment myocardial infarction can be aborted.Aim. The aim of the study was to estimate the incidence, clinical outcome, prognosis and inflammatory response in patients with aborted MI.Material and methods. 119 consecutive patients with STEMI treated with a primary percutaneous coronary intervention (pPCI) were enrolled in the study. Aborted MI was diagnosed when the maximal increase in cardiac enzymes (CK-MB) was up to twice the upper limit of normal (CK-MB ? 50 U/I) and at least 50% reduction of ST-segment deviation was observed within 90 min of pPCI.Results. Aborted MI was diagnosed in 16 subjects (13.4%). Patients with the aborted MI had lower serum troponin I levels (p &lt; 0.0001). The time to treatment was significantly shorter in the aborted MI group (101 min vs. 220 min, p &lt; 0.00001). Patients with aborted MI had a lower corrected TIMI frame count (p &lt; 0.05) and a lower wall motion score index (p &lt; 0.005), less pronounced inflammatory response (lower serum levels of IL-6, p &lt; 0.01, and MCP-1, p &lt; 0.05), higher ejection fraction six months after MI (72% vs. 64%, p &lt; 0.05). None of the aborted MI patients died during the 3-year follow-up, while there were 13 deaths among patients with non-aborted MI.Conclusions. The abortion of myocardial infarction results in a better outcome and more favorable prognosis. An inflammatory response is less pronounced in the aborted MI.

Clinical significance of cytokines levels in exhaled breath condensate (EBC) and serum of lung cancer patients.

e22202 Background: Cytokines are known to play an important role in carcinogenesis.The aim of this study is to measure pre-treatment concentrations of cytokines IL6, IL10, IL1β and IL8, in EBC and serum of lung cancer patients and to assess any possible association with clinicopathological variables and survival. Methods: From February 2010 to May 2011 we enrolled 73 patients with previously untreated lung cancer, 67 males and 6 females, age 67.7±9.5 years, 46 smokers and 27 ex-smokers, and 30 healthy individuals as controls. Sixty-one patients had NSCLC and 12 SCLC (5 stage I, 3 stage II, 19 stage III and 46 stage IV). EBC was collected using the Ecoscreen device (Viasys, Germany). Serum and EBC levels of cytokines were analyzed by commercially available enzyme-immunosorbent assay kits (ELISA). Results: All cytokines but IL8 were detectable in both materials. IL8 was not detected in EBC. All cytokines were significantly increased in patients with lung cancer in comparison to controls (IL6: serum P&lt;0.0001, EBC P=0.001; IL10: serum P= 0.006, EBC P=0.037; IL1β: serum P= 0.032, EBC P=0.005; IL8 serum P=0.001). Moreover, a statistically significant correlation was found between IL10 levels in EBC and serum (P=0.001, Rho=0.334). In EBC, higher levels of IL6 were found in patients with T3-T4 disease than in those with T1-T2 [4.27 pg/ml (2.46-5.99) vs 3.12 pg/ml (1.35-5.03), P=0.036]. Furthermore, smokers had higher serum levels of IL6 compared to ex-smokers [10.19 pg/ml (4.92-17.38) vs 4.46 pg/ml (1.88-11.53), P=0.009]. Finally, lower serum levels of IL6 &lt; median value (9.55pg/ml) were associated with improved survival (median overall survival 338 days vs 237 days Log Rank test, P= 0.046). Conclusions: Elevated levels of measured cytokines were found in both EBC and serum of lung cancer patients. Particularly, IL6 levels were related to T-stage and smoking status, while lower serum levels of IL6 with survival. These findings suggest that cytokines should be further studied in order to evaluate their diagnostic and prognostic significance. EBC could provide a simple, noninvasive and economic method for the monitoring of biomarkers in patients with lung cancer.

Biomarkers of postnatal growth in premature and full-term infants

Objective To investigate the relationship between postnatal growth of low-birth-weight (LBW) infants and different growth biomarkers including serum ghrelin, IGF-1 (reflecting anabolic activity and growth hormone sensitivity), and IL-6 (reflecting stress and inflammation). Methods This prospective study included 80 infants recruited from the Outpatient Clinic of Suzan Mubarak Specialized Hospital of Pediatrics Cairo, Egypt. They were divided into two groups: group I, comprising 40 infants who had documented LBW; and group II, comprising 40 infants with average birth weight who served as controls. Serum ghrelin level, IL-6, and IGF-1 were measured at enrollment in the study and at the end of the sixth month. Results At the onset of the study, serum ghrelin concentrations were significantly higher in infants who had LBW (group I) compared with infants who had normal birth weight (group II); P<0.001. During the follow-up period, serum levels of IGF-1 increased significantly (P<0.001). In contrast, IL-6 showed a significant decline (P<0.001) and was inversely correlated with IGF-1 (r=−0.5, P=0.003). Catch-up growth was associated with higher serum levels of ghrelin and IGF-1 and with lower serum levels of IL-6. Conclusion Catch-up growth in LBW infants is characterized by an increase in the serum ghrelin level and IGF-1 levels with a simultaneous decrease in IL-6 levels. Efforts to optimally balance inflammatory and growth mediators may benefit somatic growth in LBW infants.

Membrane-rich milk fat diet provides protection against gastrointestinal leakiness in mice treated with lipopolysaccharide

Milk fat globule membrane is a protein-lipid complex that may strengthen the gut barrier. The main objective of this study was to assess the ability of a membrane-rich milk fat diet to promote the integrity of the gut barrier and to decrease systemic inflammation in lipopolysaccharide (LPS)-challenged mice. Animals were randomly assigned to one of 2 American Institute of Nutrition (AIN)-76A formulations differing only in fat source: control diet (corn oil) and milk fat diet (anhydrous milk fat with 10% milk fat globule membrane). Each diet contained 12% calories from fat. Mice were fed diets for 5 wk, then injected with vehicle or LPS (10mg/kg of BW) and gavaged with dextran-fluorescein to assess gut barrier integrity. Serum was assayed for fluorescence 24h after gavage, and 16 serum cytokines were measured to assess the inflammatory response. Gut permeability was 1.8-fold higher in LPS-challenged mice fed the control diet compared with the milk fat diet. Furthermore, mice fed the milk fat diet and injected with LPS had lower serum levels of IL-6, IL-10, IL-17, monocyte chemotactic protein (MCP)-1, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and IL-3 compared with LPS-injected mice fed the control diet. The results indicate that the membrane-rich milk fat diet decreases the inflammatory response to a systemic LPS challenge compared with corn oil, and the effect coincides with decreased gut permeability.

An Inverse Correlation between Interleukin-6 and Select Gene Promoter Methylation in Patients with Gastric Cancer

Background: Both serum IL-6 levels and CpG island methylation have been shown to have prognostic significance in gastric cancer, it was suggested that an important link existed between IL-6 and methylation of cancers. Aim: To investigate the prognostic value of IL-6 serum level and the association between serum IL-6 levels and CpG island methylation at p16, DAPK, MGMT and E-cadherin in patients with gastric cancer. Patients and Methods: Methylation status was assessed by MSP in 75 surgical specimens of gastric adenocarcinoma. IL-6 serum levels were measured by chemiluminescent enzyme immunoassay (CLEIA). Results: Methylation of p16, DAPK, MGMT, and E-cadherin were present in 53, 48, 32, and 59% of patients. Patients with tumors methylated at p16 and DAPK had lower serum levels of IL-6 compared to unmethylated tumors (1.8 vs. 4.8 pg/ml, p = 0.01 for p16; 1.5 vs. 6.2 pg/ml, p = 0.0001 for DAPK). But there was no difference with MGMT and E-cadherin methylation status. Serum IL-6 levels were also associated with TNM stage (p = 0.001), depth of tumor invasion (p = 0.002), lymphatic invasion (p = 0.01), vascular invasion (p = 0.008), metastasis (p = 0.002) and signet cell histology (p = 0.001). Conclusion: IL-6 is of prognostic value for patients of gastric cancer. Low serum IL-6 levels were associated with p16 or DAPK gene methylation in patients with gastric cancer.

Local inhibition of endogenous IL-18 through adenoviral overexpression of IL-18BPc results in reduced incidence and severity of collagen induced arthritis in mice

IL-18 is a member of the interleukin-1 family and plays an important role in innate and acquired immunity. Previous experiments focused on IL-18 in experimental arthritis showed that neutralization through systemic treatment with either antibodies or IL-18 binding protein (IL-18BP) ameliorated the disease. To study the local role of IL-18 in arthritis we developed a replication deficient adenoviral vector containing the murine IL-18BP isoform c gene (Ad5CMV.IL-18BPc). The neutralizing ability of adenoviral overexpressed IL-18BPc on IL-18 response was tested in vitro. Supernatants of IL-18BP transfected cells significantly inhibited IL-18 induced luciferase production in IL-18 sensitive NFkB luciferase reporter fibroblasts. Next we injected 1 × 107PFU of Ad5CMV.IL-18BPc or the control vector Ad5CMV.Luc into the murine knee joint cavity of DBA/1 mice before onset of collagen-induced arthritis (CIA). IL-18BPc overexpression significantly reduced local knee joint swelling in CIA with 66% (P < 0.001) and distal paw swelling with approx. 50% (P < 0.01) compared to the control vector. Furthermore, local IL-18BPc resulted in lower serum levels of IL-6 compared to the control (respectively 5.0 pg/ml and 12.7 pg/ml, P < 0.001). Serum titers of specific IgG1, IgG2a and total IgG antibodies directed towards collagen type II showed no significant differences between control and IL-18BPc treatment, indicating that the effect seen on arthritis by overexpression of IL-18BPc in the joint was not caused by an IL-18BPc effect on humoral immunity. These results clearly show that IL-18 present in the arthritic joint plays an important proinflammatory role and demonstrate that adenoviral overexpression of IL-18BPc in the synovium is an efficacious local treatment in experimental arthritis.