Blood Levels Of IL-6 Research Articles

Systematic reviews of effects of Tripterygium Glycosides Tablets on pro-inflammatory factors in rheumatoid arthritis

To systematically evaluate the effects of Tripterygium Glycosides Tablets alone or in combination with methotrexate(MTX) and leflunomide(LEF) on the levels of pro-inflammatory cytokines in patients or animal models with rheumatoid arthritis(RA), and to provide reference for clinical application and related basic research, this study systematically searched databases of CNKI, VIP, WanFang, PubMed, Embase and Cochrane Library, collected relevant clinical or animal experimental studies, used risk assessment tools to evaluate the quality of research, and used Revman 5.3 software to conduct Meta-analysis or descriptive analysis of the outcome indicators included in the literatures. Of the 1 709 papers retrieved, 3 clinical studies and 12 animal experiments were included. The results showed that compared with MTX alone, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of peripheral blood TNF-α(SMD=-8.88,95%CI[-10.77,-6.99],P<0.000 01),IL-1β(P<0.000 01) and IL-6(SMD=-8.63, 95%CI[-10.57,-6.69], P<0.000 01) in RA patients. Compared with LEF alone, the combination of Tripterygium Glycosides Tablets and LEF could not further reduce the expression levels of TNF-α(P=0.20), IL-1β(P=0.17), IL-6(P=0.31). In RA animal model, compared with model group, Tripterygium Glycosides Tablets could reduce the expression levels of peripheral blood IL-1β(SMD=-6.29,95%CI[-9.64,-2.93],P<0.000 2)in peripheral blood(SMD=-1.39,95%CI[-1.77,-1.02],P<0.000 01), joint fluid(P<0.000 01) and paw plasma(P=0.02), and also reduce the expression levels of TNF-α in RA animal model group. Compared with MTX alone, Tripterygium Glycosides Tablets alone reduced the same levels of TNF-α(P=0.42) and IL-6(P=0.08) in joint fluid, while Tripterygium Glycosides Tablets combined with MTX could further reduce the levels of IL-6(P=0.000 1) in joint fluid; compared with LEF alone, Tripterygium Glycosides Tablets have the similar effects on reducing the expression levels of peripheral blood TNF-α(P=0.16), IL-1β(P=0.32), IL-6(P=0.12), while Tripterygium Glycosides Tablets combined with LEF could further reduce the expression levels of TNF-α(P=0.008), IL-1β(P=0.02), IL-6(P<0.000 1) in peripheral blood. Therefore, Tripterygium Glycosides Tablets combined with MTX could further reduce the expression levels of pro-inflammatory cytokines in peripheral blood of RA patients. Tripterygium Glycosides Tablets alone could reduce the expression levels of pro-inflammatory cytokines in peripheral blood and local joint of RA animal models. Tripterygium Glycosides Tablets combined with MTX or LEF could further reduce the express levels of pro-inflammatory cytokines in peripheral blood of RA animal models. Due to the limitation of literature, this conclusion needs to be further validated.

The potential mechanism of INHBC and CSF1R in diabetic nephropathy.

The aim of this study was to research the potential mechanism of INHBC and CSF1R in diabetic nephropathy. 30 SD rats were selected and randomly divided into Con group, Sham group, and DN group. In the DN group, intraperitoneal injection of the streptozotocin-citrate solution was conducted to construct the DN model. In the Sham group, intraperitoneal injection of equal citrate solution was conducted. The Con group did not do anything. After successful modeling, blood glucose, insulin, biochemical indexes, and levels of inflammatory cytokines in blood samples were detected. The expression levels of INHBC, CSF1R, apoptosis-related proteins and IGF-1 were detected by Western blot. MRNA expression levels of INHBC, CSF1R, IGF-1 and inflammatory cytokines were detected by qPCR. Compared with the Con group, the expression levels of blood glucose, insulin, biochemical indexes, INHBC, CSF1R, IGF-1, IL-6, TNF-α and Bcl2 increased in the DN group, while the expression levels of IL-10, Caspase 3, Caspase 9, and Bax decreased. INHBC mRNA was positively correlated with IGF-1 mRNA. CSF1R was negatively correlated with Caspase 3, Caspase 9, Bax, and IL-10, and positively correlated with IL-6, TNF-α, and Bcl2. NHBC and CSF1R induced the secretion of IL-6 and TNF-α, inhibited the production of IL-10, inhibited apoptosis of cells, and promoted the proliferation of renal cells during DN disease. Therefore, INHBC and CSF1R can be used as target objects of DN treatment strategies.

Efficacy of acupuncture at three nasal acupoints plus acupoint application for perennial allergic rhinitis: A multicenter, randomized controlled trial protocol

BackgroundMany studies have shown the potential therapeutic effect of acupuncture on allergic rhinitis. Most of these studies were limited by low-quality evidence. Preliminary experiments showed that the use of acupuncture at three nasal acupoints plus acupoint application (AAP) achieves a more persistent effect in the treatment of perennial allergic rhinitis than acupuncture alone. In this study, a multicenter, single-blind, randomized controlled trial will be performed, in which acupuncture at nonmeridian acupoints and sham AAP will be used as the control group to evaluate the effect of AAP through long-term observation.MethodsThe trial is designed on the basis of the Consolidated Standards of Reporting Trials 2010 guidelines and Standards for Reporting Interventions in Controlled Trials of Acupuncture. A total of 120 participants with perennial allergic rhinitis will be randomly assigned to a treatment or control group. A specially appointed investigator will be in charge of randomization. The participants in the treatment group will be treated with acupuncture at EX-HN3, LI20, and EX-HN8 thrice per week for a total of 12 sessions. In addition, they will undergo AAP at DU14, BL13, EX-BI, and RN22. The participants in the control group will be treated with sham AAP. The primary outcome will be the change in the Total Nasal Symptom Score from baseline to the completion of 4-week treatment. Secondary outcomes include changes in visual analog scale and total non-nasal symptom scores from baseline to the second and fourth weeks of treatment, as well as 1, 3, and 6 months after the completion of treatment. Peripheral blood IL-4, IL-5, IL-6, IL-8, and IL-10 levels will be measured, and any side effects related to treatment will be observed and recorded.DiscussionIt is expected that this randomized clinical trial will provide evidence to determine the effects of AAP compared with acupuncture at nonmeridian acupoints and sham AAP, particularly the long-term effect. These findings will help improve the clinical application of this technique.Trial registrationAcupuncture-Moxibustion Clinical Trial Registry AMCTR-ICR-18000179. Registered on 12 April 2018.

İntrabdominal Sepsisli Hastalarda Serum Adıponektin Sevıyeleri İle Proinflamatuar Sitokin Düzeyleri, Apache-II Skorları ve Mortalite Arasındaki İlişki

Objectives: Adiponectin is an anti-inflammatory cytokine that is abundantly produced by adipocytes and have a wide range of effects in sepsis pathophysiology. This study was conducted to investigate whether there is a correlation between serum adiponectin, proinflammatory cytokines’ levels, APACHE-II scores and mortality rates of the patients with sepsis, severe sepsis and septic shock. Patients and Methods: Forty-five patients who met the criteria for sepsis n=18 , severe sepsis n=14 and septic shock n=13 were included in this prospective study. Patients who underwent elective abdominal surgery without sepsis were identified as the control group. After the diagnosis of sepsis, blood samples were taken on the following 5 days for adiponectin, IL-6, IL-1β, TNF-α and procalcitonin levels. APACHE-II scores of the patients were calculated daily. All patients were followed for 28 days and mortalities were observed. Results: Ten of the patients died within 28 days. The serum adiponectin levels of the patients in the study group were statistically higher than those in the control group. Statistically, the adiponectin levels of the patients in the septic shock group were markedly lower than those of the patients in sepsis and severe sepsis groups. Serum adiponectin levels inversely correlated with blood levels of IL-6, IL-1β, TNF-α, procalcitonin, lactate and APACHE-II scores. Serum adiponectin levels were significantly higher in survivors. Conclusion: Adiponectin levels reveal differences between sepsis, severe sepsis and septic shock groups. In patients with septic shock, serum adiponectin levels were associated with mortality among patients. Serum adiponectin levels might be a negative predictive marker in patients with sepsis, severe sepsis and septic shock.

ОСОБЕННОСТИ ЦИТОКИНОВОГО ПРОФИЛЯ У ОЖОГОВЫХ ПАЦИЕНТОВ

Introduction. Currently, more and more attention is paid to burn injury as one of the most significant medical and social problems. Treatment of burn injury is performed by autotransplantation of the skin flap. The efficiency of using this method is from 70 to 90%. A significant reason for the failure of skin flap transplantation in burn disease is the lack of objective methods for assessing the patient's condition on the eve of free autodermoplasty surgery. Assessment of the levels of both Pro-and anti-inflammatory cytokines in burned patients is not included in the algorithm of examination and monitoring of the status of these patients. The aim of the study: to study the levels of pro — and anti-inflammatory cytokines to expand the algorithm of laboratory examination in preparing patients for free autodermoplasty.Materials and methods. The levels of IL-6, IL-8, and IL-10 in the peripheral blood of 50 patients with burn injury compared to healthy individuals were studied by enzyme immunoassay. Results. The serum content of all studied cytokines was significantly increased upon admission to the hospital in all burn patients compared to healthy individuals. A particularly pronounced increase was observed in patients with a fatal outcome. The results of autodermoplasty correlated with the severity of hyperproduction of proinflammatory cytokines on the eve of surgery. Conclusion. A justification for the addition of the algorithm for laboratory examination of burned patients by determining cytokines-interleukins 6, 8 and 10. Monitoring the level of cytokines in burn injury is appropriate for objectifying the choice of the timing of surgery, which will help reduce the mortality rate and increase the effectiveness of free autodermoplasty.

A connection between arterial hypertension, dyslipidemia and activity of interleukin-1β and interleukin-6 IN type 2 diabetes mellitus

To determine the relationship between blood pressure (BP), lipid metabolism and levels of IL-1β and IL-6 in patients with type 2 diabetes mellitus (T2DM). Ninety six patients with T2DM (mean age 52.74 ± 9.56, 38 women) were examined, and 20 healthy volunteers. A systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured; levels of total cholesterol (TC), high density lipoprotein cholesterol (HDL), triglycerides (TG), low density lipoprotein cholesterol (LDL)were determined. The levels of IL-1-β and IL-6 were determined by the immune-enzymatic method. SBP (mm Hg) in main group − 141.76 ± 1.31, in control group - 120.75 ± 1.51; DAT (mm Hg)–88.43 ± 0.68 and 77.75 ± 0.85, respectively; MAP −106.23 ± 0.87 and 92.08 ± 0.98, respectively ( P < 0.05). TC (mmol/L) in the main group was 5.29 ± 0.15, in the control group − 4,06 ± 0.05; TG (mmol/L) 1.20 ± 0.02 and 1.3 ± 0.03, respectively; LDL (mmol/L) 3.28 ± 0.14 and 2.01 ± 0.04, respectively ( P < 0.05). IL-1β (ng/mL) in main group was 13.58 ± 0.29, control group − 8.12 ± 0.24; IL-6 (ng/mL) 12.37 ± 0.3 and 8.83 ± 0.22, respectively ( P < 0.05). Significant correlations were revealed between the studied indices in the main group: SBP and TC ( r = 0.29), SBP and TG ( r = 0.28), SBP and LDL ( r = 0.28), SBP and IL-1β ( r = 0.41), SBP and IL-6 ( r = 0.25); DBT and IL-1β ( r = 0.25); MAP and TC ( r = 0.26), MAP and TG ( r = 0.29), MAP and LDL ( r = 0.27), MAP and IL-1β ( r = 0.39), MAP and IL-6 ( r = 0.28). There were no significant correlations in the control group. The revealed interrelations indicate that the risk of arterial hypertension is increased even with a slight elevation of BP in patients with T2DM. The reasons for this include not only the increase of vascular resistance and the decrease of the elasticity of the vascular wall, but also the progression of dyslipidemia and deployment of systemic inflammatory response due to the increased levels of proinflammatory cytokines IL-1β and IL-6.

Longitudinal Characteristics of Lymphocyte Responses and Cytokine Profiles in the Peripheral Blood of SARS-CoV-2 Infected Patients

Background: The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Method: Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. Findings: Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts but increases in neutrophil counts than 27 mild cases. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8 + T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-CD8+ T cell ratio (N8R) were identified as the most powerful prognostic factor affecting the prognosis for severe COVID-19. Interpretation: The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R may serve as a useful prognostic factor for early identification of severe COVID-19 cases. Funding Statement: This work is supported by the National Natural Science Foundation of China (81861138044, 91742114 and 91642118), the National Science and Technology Major Project (2018ZX10723203, 2018ZX10302206, 2017ZX10202201, 2017ZX10202202 and 2017ZX10202203), the Innovation Team Project of Health Commission of Hubei Province (WJ2019C003), the Integrated Innovative Team for Major Human Diseases Program of Tongji Medical College and the “Double-First Class” Project for the International Cooperation Center on Infection and Immunity, HUST, and a special joint project of University Hospital Essen, University of Duisburg-Essen. Declaration of Interests: The authors disclose no conflicts of interest. Ethics Approval Statement: A written informed consent was regularly obtained from all patients upon admission into Wuhan Union Hospital, China. The study was approved by the Ethics Committee of Tongji Medical College of Huazhong University of Science and Technology.

Examination of Intrauterine Inflammation and Immature Platelet Fraction at Birth in Extremely Low Birth Weight Infants

IL-6 is thought to be involved in the prognosis of extremely low birth weight infants, in whom it leads to newborn organopathy. IL-6 also influences various processes <i>in vivo</i>, including thrombocytopoiesis. In the present study, we investigated whether the influence of IL-6 in the fetal period could be evaluated using the actual number of infant platelets, which is an index of thrombocytopoiesis. We retrospectively examined the perinatal information of extremely low birth weight infants, IL-6, the number of platelets (Plt), and the number of immature platelets fraction (IPF). The study population included 81 infants. The mean gestational age of the infants was 26.1±2.5 weeks and the mean birth weight was 729±161 g. The immature platelet count (Plt×IPF) was positively correlated with the IgM level (R=0.45, p<0.01) and the membrane rupture time (R=0.095, p<0.01). In addition, the Plt×IPF in the group in which the cord blood IL-6 level was ≥11 pg/mL was significantly higher than that in the group in which the cord blood IL-6 was <11 pg/mL (p<0.01). The Plt×IPF value at birth was associated with the IL-6 level in extremely low birth weight infants, which suggests the possibility that it may be used to evaluate fetal inflammation.

Leucine 섭취와 저항 운동이 Adipokine 및 염증 반응에 미치는 영향

The purpose of this study was to examine the effects of resistance training with leucine supplementation on adipokine and inflammatory response in college-aged obese men. Thirty collegeaged obese man were randomly assigned to resistance training group(RT group, n=15), and resistance training with leucine supplementation group(RTL group, n=15). The experiments were performed after taking consent form from each subjects. Resistance training program was consisted of bench press, leg press and curl, back squat, and deadlift. Participants performed resistance training three days per week for 4 weeks. Exercise intensity of this resistance training was 75% 1RM of each exercise program. Body weight showed significant difference between time in the both group. % body fat and fat mass showed significant difference between time in the RT group(p.05). Blood level of leptin decreased after 4 weeks resistance training in RT groups(p.05), however blood level of adiponectin increased after 4 weeks resistance training in both groups. The blood level of TNF-α decreased after 4 weeks resistance training in RT group(p.05), but the blood level of IL-6 was not changed after 4 weeks resistance training in both groups(p.05). In conclusion, regularly resistance training have positive effects on body composition, adipokine, and TNF-α.

Effect of Serum Ammonia, TNF-Alfa and IL-6 Levels on the Degree and Outcome of Hepatic Encephalopathy in Egyptian Cirrhotic Patients

Abstract Background: Hepatic Encephalopathy (HE) is a major complication of liver cirrhosis characterized with neuropsy-chiatric symptoms it's etiology is multifactorial. Aim of Study: Aim of the study serum ammonia, TNF-alfa and IL-6 levels on the degree and outcome of hepatic encephalopathy in Egyptian cirrhotic patients. Patient and Methods: The study included 90 patients with liver cirrhosis complicated with HE (patients group) and 60 cirrhotic patients without HE as control group (group 3), the patients group divided into subgroups according to the grade of encephalopathy from the beginning the study, group A encephalopathy: Grade 1 and 2 and group B encephalopathy: Grade 3 and 4. All patients were followed-up for 7 days, then divided into 2 groups according to the response to treatment; group 1: Complete recovery and group 2: With improper response. Results: There were statistical difference between patients groups (group 1and 2) and control group (group 3) in terms of blood ammonia levels (67.5±22.5, 13±4.8), serum TNF-a levels (21.6±3.2, 2.3±.2) and mean serum IL-6 (63.9±15.9, 4±1.29) respectively. There were statistical difference between group 1 and group 2 in terms blood ammonia levels (46±12.8, 86.5±30.5), mean serum TNF-a levels (7.1±2.9, 29.4±13.3) and mean serum IL-6 (19±9.2, 93.9±20.9). Results also, showed statistical significant difference between group 2A and group 2B in terms of blood ammonia level (79.2±20.6, 173.7±38.7), mean serum TNF-a levels (18.1±5.3, 39.9±14.5) and mean serum IL-6 levels (69.2±11.1, 118.2±13.8). In group 2 there were significant positive correlation between serum TNF with blood ammonia level (r=0.843, p=0.001), serum IL-6 (r=0.732, p=0.001) and between IL-6 and blood ammonia level (r=0.699, p=0.001). Conclusion: There is a strong relation between high blood level of ammonia, TNF alfa, IL-6 and grade and outcome of HE in cirrhotic patients.

The Lymphoma Tumor Microenvironment Influences Toxicity after CD19 CAR T Cell Therapy

Introduction: Of patients receiving CD19 CAR T cell therapy for large B cell lymphoma (LBCL), approximately 1 in 10 experience severe cytokine release syndrome (CRS) and 1 in 3 experience severe neurotoxicity. While CAR T cells trigger the onset of these toxicities, CRS and neurotoxicity are thought to occur as a consequence of activated myeloid cells amplifying cytokine and catecholamine release, thereby stimulating inflammation both systemically and at the blood-brain barrier. However, patient and tumor-related factors that account for differences in the amount of toxicity remain poorly understood. Methods: Serum cytokine levels were measured on an ELLA point of care device prior to lymphodepleting chemotherapy and throughout inpatient treatment with CD19 CAR T cell therapy (axicabtagene ciloleucel) for LBCL. Catecholamine levels were measured as we have previously reported. Tumor biopsies were taken within 1 month prior to infusion of CAR T cells. RNA expression was measured by RNAseq and/or a Nanostring IO360 panel consisting of 770 genes found in the tumor microenvironment (TME) in cancer. Analysis used nSolver to identify cell types, GSEA and differential gene expression between groups. Mouse CAR T cell studies utilized mouse CD19-targeted CAR T cells derived from C57BL/6 splenocytes and cultured in vitro with myeloid cells and target cells to evaluate cytotoxicity and/or cytokine secretion. Elicited mouse macrophages were collected from peritoneal fluid 4 days after IP injection of 3% Brewer's thioglycollate medium. In vivo studies with mouse CD19-targeted CAR T cells were performed in IL2Ra-/- mice given cyclophosphamide as a pre-conditioning chemotherapy followed by adoptive transfer and analyses for CAR T cell and B cell persistence, as well as cytokines. Results: Of 58 patients undergoing CD19 CAR T cell therapy for LBCL, 8 (14%) had severe (grade 3 or higher) CRS and 16 (28%) had severe (grade 3 or higher) neurotoxicity. At baseline, peripheral blood levels of IL-6, IFN-γ, IL-15 and ferritin were significantly higher in patients who would subsequently experience severe CRS and severe neurotoxicity. Confirming our recent animal model of CRS we determined that peak serum catecholamine levels were higher in patients experiencing severe CRS. To identify if myeloid cells potentiate cytokine release we co-cultured CAR T cells with CD19 target and macrophages obtained from elicited mouse peritoneum. When these macrophages were added, IL-6 release from CAR T cells significantly increased compared to when macrophages were absent. Next, we studied the baseline TME in LBCL CAR T patients. Of 36 patients, 10 (27%) experienced severe neurotoxicity following CAR T cell therapy. By cell type score, the severe neurotoxicity group had a lower expression of genes associated with T cells overall and specifically Tregs. Also significantly lower in the severe neurotoxicity group were T cell genes including multiple subunits of CD3, CD3ζ, FOXP3, ICOS, CD62L and others. Association of increased T cell infiltration in the TME with low neurotoxicity raised the possibility that suppressive T cell subsets play a role in limiting toxicity post-CAR T cell therapy. To test this hypothesis, we injected CD19-targeted CAR T cells into an immune competent mouse model of Treg depletion (IL2Ra-/-) with established CD19+ leukemia. Treg deficient mice experienced a massive cytokine release after CAR T infusion and died prematurely due to CAR T toxicity compared to control mice with Tregs intact. Conclusions: Our observations suggest that the incidence of severe toxicity following CD19 CAR T cell therapy is influenced by baseline characteristics that are present prior to the infusion of CAR T cells. These include systemic inflammation characterized by high cytokine levels and a TME notable for a lack of infiltrating T cells. We posit a model whereby inflammation primes myeloid cells that are further activated upon CAR T cell infusion to release toxic amounts of cytokines and catecholamines. T cell subsets in the TME may modulate CAR T cells at the site of antigen encounter and prevent excessive CAR T activation. Reducing systemic inflammation or encouraging T cell infiltration into tumor prior to CAR T infusion are potential strategies for lowering the toxicity associated with CAR T therapy. Disclosures Jain: Kite/Gilead: Consultancy. Chavez:Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Genentech: Speakers Bureau; Janssen Pharmaceuticals, Inc.: Speakers Bureau. Shah:Novartis: Honoraria; Spectrum/Astrotech: Honoraria; Celgene/Juno: Honoraria; Kite/Gilead: Honoraria; Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Pharmacyclics: Honoraria; Adaptive Biotechnologies: Honoraria; AstraZeneca: Honoraria. Bachmeier:Kite/Gilead: Speakers Bureau. Mullinax:Iovance: Research Funding. Locke:Novartis: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy; Kite: Other: Scientific Advisor. Davila:Anixa: Consultancy; Precision Biosciences: Consultancy; Novartis: Research Funding; GlaxoSmithKline: Consultancy; Adaptive: Consultancy; Celgene: Research Funding; Atara: Research Funding; Bellicum: Consultancy.

Cytokine Profile in Early Infection by Leptospira interrogans in A/J Mice.

Leptospirosis is considered a neglected disease with an estimated more than one million cases every year. Since rodents are at the same time the main reservoir and generally asymptomatic to Leptospira infection, understanding why some animal species are resistant and others are susceptible to this infection would shed some light in how to control this important zoonosis. The innate immune response against Leptospira is mainly dependent on phagocytosis and activation of the Complement System. In this context, cytokines may drive the early control of infection and the adaptive response. Since the Complement System is important to eliminate leptospires in vivo, we investigated if Complement C5 in A/J mice would modulate the cytokine production during infection by Leptospira interrogans serovar Kennewicki type Pomona Fromm (LPF). Thus, our aim was to investigate the systemic levels of pro- and anti-inflammatory cytokines during Leptospira infection in the blood, liver, lung, and kidney on the third and sixth days of infection in A/J C5+/+ and A/J C5−/− mice. Blood levels of TNF-α, IL-6, IFN-γ, and MCP-1 reached a peak on the third day. Although both mouse strains developed splenomegaly, similar histopathological alterations in the liver and the lung, levels of pro- and anti-inflammatory cytokines were different. A/J C5+/+ mice had higher levels of liver IL-10, IL-1β, IL-12p40, and IL-12p70 and kidney IL-1β, IL-12p40, and IL-12p70 on the sixth day of infection when compared to A/J C5−/− mice. Our results showed that in A/J genetic background, the Complement component C5 modulates a cytokine profile in the liver and kidney of infected mice, which may play a role in the control of disease progression.

Urinary NGAL and RBP Are Biomarkers of Normoalbuminuric Renal Insufficiency in Type 2 Diabetes Mellitus.

Objectives As a screening index of diabetic kidney disease (DKD), urinary albumin/creatine ratio (UACR) is commonly used. However, approximately 23.3%-56.6% of DKD patients with estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 are normoalbuminuric. Thus, urinary biomarkers of nonalbuminuric renal insufficiency in type 2 diabetes mellitus (T2DM) patients are urgently needed. Methods This cross-sectional study enrolled 209 T2DM patients with normoalbuminuria whose diabetes duration was more than 5 years. The patients were classified into two groups, NO-CKD (eGFR ≥ 60 ml/min per 1.73 m2, n = 165) and NA-DKD (eGFR < 60 ml/min per 1.73 m2, n = 44). Levels of urinary neutrophil gelatinase-associated lipocalin (NGAL), retinol-binding protein (RBP), plasminogen activator inhibitor-1 (PAI-1), vascular cell adhesion molecule-1 (VCAM-1), and E-cadherin were detected, and their correlations with eGFR, plasma TNF-α, IL-6, endothelin-1 (ET-1), and 8-hydroxydeoxyguanosine (8-OHdG) were assessed. Results Among patients with renal insufficiency, 26.0% was normoalbuminuric. Compared to the NO-CKD group, the NA-DKD group was older with lower hemoglobin (HB) levels and higher systolic blood pressure (SBP), plasma TNF-α, IL-6, and 8-OHdG levels. Logistic regression analysis suggested that age, TNF-α, and 8-OHdG were independent risk factors for nonalbuminuric renal insufficiency. Compared to the NO-CKD group, the NA-DKD group exhibited significant increases in urinary NGAL and RBP levels but not PAI-1, VCAM-1, and E-cadherin. Urinary NGAL and RBP both correlated negatively with eGFR and positively with plasma IL-6 and 8-OHdG. Multiple linear regression indicated NGAL (β = −0.287, p = 0.008) and RBP (β = −44.545, p < 0.001) were independently correlated with eGFR. Conclusion Age, plasma TNF-α, and 8-OHdG are independent risk factors for renal insufficiency in T2DM patients with normoalbuminuria. Urinary NGAL and RBP can serve as noninvasive biomarkers of normoalbuminuric renal insufficiency in T2DM.

Short-term efficacy and safety of prednisone in herpes zoster and the effects on IL-6 and IL-10.

Short-term efficacy and safety of prednisone in herpes zoster and the effect on IL-6 and IL-10 were investigated. A total of 125 patients (aged 40–70 years) with acute infective herpes zoster who were admitted to Daqing Oilfield General Hospital were selected and divided into 3 groups according to different treatment methods: low-dose (n=44), middle-dose (n=42) and high-dose (n=39) groups. The therapeutic effect, visual analogue scale (VAS) pain score, pain relieving and disappearing time, herpes stopping and disappearing time, incrustation and decrustation time, and incidence of adverse reactions in the three groups were recorded. The changes of IL-6 and IL-10 levels in the peripheral blood of patients before and after treatment were detected by enzyme-linked immunosorbent assay (ELISA) in order to analyze their relationship with pain degree and the time of symptom remission and subsidence. There were no significant differences in cure rate, significant effective rate, effective rate, ineffective rate and total effective rate among the three groups (P>0.05). The pain relieving and disappearing time in the middle-dose group were shorter than those in the low- and high-dose groups (P<0.05). The levels of IL-6 and IL-10 showed no statistical differences in the 3 groups before treatment (P>0.05). Pearson correlation analysis showed that IL-6 was positively correlated with VAS pain score, pain relieving and disappearing time, herpes stopping and disappearing time, incrustation and decrustation time (P<0.05), while IL-10 was negatively correlated with the above indicators (P<0.05). In conclusion, middle-dose prednisone has similar short-term efficacy to high-dose prednisone in the treatment of herpes zoster, but with lower complication and higher safety. IL-6 and IL-10 are closely related to the pain degree and the time of symptom remission and subsidence, which may provide a reference for clinical evaluation of the therapeutic effect of patients with herpes zoster.

Using Interleukin 6 and 8 in Blood and Bronchoalveolar Lavage Fluid to Predict Survival in Hematological Malignancy Patients With Suspected Pulmonary Mold Infection.

Background: Molds and other pathogens induce elevated levels of several cytokines, including interleukin (IL)-6 and IL-8. The objective of this study was to investigate the prognostic value of IL-6 and IL-8 as well as fungal biomarkers in blood and bronchoalveolar lavage fluid (BAL) for overall survival in patients with underlying hematological malignancies and suspected mold infection.Methods: This cohort study included 106 prospectively enrolled adult cases undergoing bronchoscopy. Blood samples were collected within 24 h of BAL sampling and, in a subset of 62 patients, serial blood samples were collected up until 4 days after bronchoscopy. IL-6, IL-8, and other cytokines as well as galactomannan (GM) and β-D-glucan (BDG) were assayed in blood and BAL fluid and associations with overall mortality were assessed at the end of the study using receiver operating characteristic (ROC) curve analysis.Results: Both blood IL-8 (AUC 0.731) and blood IL-6 (AUC 0.699) as well as BAL IL-6 (AUC 0.763) and BAL IL-8 (AUC 0.700) levels at the time of bronchoscopy were predictors of 30-day all-cause mortality. Increasing blood IL-6 levels between bronchoscopy and day four after bronchoscopy were significantly associated with higher 90-day mortality, with similar findings for increasing IL-8 levels. In ROC analysis the difference of blood IL-8 levels between 4 days after bronchoscopy and the day of bronchoscopy had an AUC of 0.829 (95%CI 0.71–0.95; p < 0.001) for predicting 90-day mortality.Conclusions: Elevated levels of IL-6 and IL-8 in blood or BAL fluid at the time of bronchoscopy, and rising levels in blood 4 days following bronchoscopy were predictive of mortality in these patients with underlying hematological malignancy who underwent bronchoscopy for suspected mold infection.

Correlation study of peripheral blood inflammatory factors in patients with sudden deafness

Objective:The aim of this study is to compare the difference of inflammatory factors in peripheral blood between sudden deafness patients and normal people, and to evaluate the predictive value of inflammatory factors in hearing recovery of sudden deafness patients. Method:Seventy-two inpatients with sudden deafness and 19 healthy persons were included. At the beginning of treatment in our hospital, audiometry was performed and peripheral blood was collected. The levels of IL-1β, IL-6, IL-17α, TGF-β1 and TNF-α in peripheral blood were detected by ELISA. The treatment was intravenous steroid（not applied if patients with contraindication of systemic steroid application）+ intratympanic steroid injection+ microcirculation improvement or neurotrophic therapy+ hyperbaric oxygen. At the end of the treatment, audiometry was performed again. A total of 26 patients were collected to test the levels of inflammatory factors in peripheral blood again at the end of the treatment. Result:The mean levels of inflammatory factors IL-1β, IL-6, IL-17α, TGF-β1 and TNF-α in peripheral blood of patients were （2.66±9.57） pg/ml, （4.71±6.91） pg/ml, （19.33±32.27） pg/ml, （50 018.37±14 660.72） pg/ml, （1.52±2.40） pg/ml, respectively. And the level of these five inflammatory factors in normal persons were （3.61±9.82） pg/ml, （3.58±4.49） pg/ml, （11.64±13.29） pg/ml, （45 199.98±11 956.09） pg/ml，（1.09±1.08） pg/ml respectively. Statistical analysis showed no significant difference between these two groups. A total of 45 cases were effective（hearing threshold increased ≥15 dB） and 27 cases were ineffective（hearing threshold increased<15 dB）. There was no significant difference in the levels of inflammatory factors between the two groups. Among 26 patients with blood samples before and after treatment, the level of TGF-β1 after treatment was significantly lower than that before treatment. Conclusion:The levels of these five inflammatory factors including IL-1β, IL-6, IL-17α, TGF-β1 and TNF-αin peripheral blood could not predict the recovery of sudden hearing loss. The role of inflammation in the development of sudden deafness needs further confirmation. TGF-β1 may be involved in the development of sudden deafness.

Pollen Allergy Suppression Effect by the Oral Administration of Acetic Acid Bacteria (Gluconacetobacter hansenii).

Gluconacetobacter hansenii (G. hansenii) is an acetic acid bacterium of vinegar production. Its anti-allergic effect on mice upon oral administration was examined. The amount of LPS was measured by the Limulus reaction. Mice were sensitized by peritoneal and intranasal administration of cedar pollen and alum followed by oral administration of 30 or 150 mg/kg of heated G. hansenii cells. Pollen was administered intranasally to evaluate nasal symptoms, and at 8 weeks, IgE and IL-10 levels in blood were measured by ELISA. The amount of LPS in dried bacterial cells was 10.4±3.3 mg/g. In the cedar pollinosis model of mice, a significant reduction was observed in nose scratching of both groups administered with the bacterial cells (30, 150 mg/kg). G. hansenii contains LPS, and its oral administration showed an anti-allergic effect by a significant mitigation of the symptoms in a pollen allergy mouse model.

Diagnostic efficacy of serum procalcitonin, IL-6, IL-2, and D-dimer levels in an experimental acute appendicitis model.

Acute appendicitis is the most frequent cause of acute abdomen emergency surgery. It continues to be a problem today due to delayed diagnosis and its high perforation rate. For this reason, diagnostic tests continue to be developed. In this experimental study, the diagnostic significance of blood procalcitonin (PCT), interleukin (IL)-6, IL-2, and D-dimer levels in an acute appendicitis model in rabbits was investigated. A total of five groups were included: control group, sham group, and three different acute appendicitis groups. In the appendicitis groups, the appendix was ligated by laparotomy, and the blood PCT, IL-6, IL-2, and D-dimer levels were measured at 12 (group 3), 24 (group 4), and 48 h (group 5). Then, an appendectomy was performed. In the present study, PCT and IL-6 levels increased in parallel with the inflammation of the appendix in all groups and were found to be statistically significant. IL-2 and D-dimer values were higher in the groups diagnosed with appendicitis but were not statistically significant. In our experimental study, PCT and IL-6 levels were determined to be important in the early diagnosis of acute appendicitis, especially IL-6, and that these two parameters are more important markers than IL-2 and D-dimer.

Abstract 1344: IL-6 blood level represents an independent biomarker of melanoma patient prognosis

Abstract IL-6 is an inflammatory cytokine produced by both immune and tumor cells, including melanoma cells. IL-6 has been shown to stimulate melanoma growth and invasiveness, and blood levels of IL-6 have been proposed as a melanoma prognostic marker. We previously provided validated evidence that CRP, downstream of IL-6 in the inflammatory cascade, is an independent blood biomarker of melanoma patient prognosis. In the current study, we performed coordinated evaluation of blood levels of both CRP and IL-6 in a large cohort of melanoma patients evaluated and treated at a comprehensive cancer center for whom consistent evaluation, staging, treatment and follow-up were performed. 473 patients underwent blood draw following melanoma diagnosis. There were 177 female and 296 male patients. Median age at blood draw was 58. Median primary tumor thickness was 1.39 mm and 29% of tumors were ulcerated. At blood draw, 187 patients were stage I/II and 286 were stage III/IV. Median follow-up from blood draw was 25 months. There were 60 deaths during follow-up, including 37 melanoma-related deaths. Plasma IL-6 and CRP levels were determined using Elisa kits (R&amp;D Systems). Outcome measures (overall survival, OS; melanoma-specific survival, MSS) were determined from the date of blood draw. On univariate analysis, an elevated level of IL-6 was associated with elevated age at blood draw (Spearman correlation coefficient (CC) 0.2190, P&amp;lt;0.0001), increased tumor thickness (CC 0.2450, P&amp;lt;0.0001), advanced stage at blood draw (ANOVA P=0.01), decreased OS from blood draw (Cox P=0.0001), and decreased MSS from blood draw (Cox P&amp;lt;0.0001). IL-6 levels were highly correlated with CRP levels (CC 0.680, P&amp;lt;0.0001), and on univariate analysis CRP demonstrated similar patterns to IL-6 with regards to age, stage and outcome measures. In a multivariate model that included age, sex, stage, IL-6 and CRP, elevated IL-6 was an independent predictor of shorter OS (HR 1.72, 95% CI 1.39-2.13; Cox P&amp;lt;0.0001), while CRP was not. Additionally, in a multivariate model of MSS, elevated IL-6 was an independent predictor of shorter OS (HR 2.24, 95% CI 1.73-2.89; Cox P&amp;lt;0.0001), while CRP was not. In summary, in a large cohort of melanoma patients, blood level of IL-6 was a strong and consistent predictor of important outcome measures, including OS and MSS. Furthermore, predictions of patient outcomes remained robust following adjustment for important covariates, including the clinicopathologic predictors of age, sex, and stage, as well as the downstream inflammatory biomarker CRP. These results suggest that IL-6 is a clinically relevant inflammatory biomarker in melanoma patients, and that the previously identified association of CRP with melanoma patient outcome is likely downstream and secondary to the effect of IL-6. Prospective investigations are ongoing, including of the potential predictive role of IL-6 in melanoma patients treated with targeted and immune-based therapies. Citation Format: Yuling Wang, Dawen Sui, Kejing Xu, Lauren E. Haydu, Shenying Fang, Merrick I. Ross, Jeffrey E. Gershenwald, Jeffrey E. Lee. IL-6 blood level represents an independent biomarker of melanoma patient prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1344.

A CONNECTION BETWEEN ARTERIAL HYPERTENSION, DYSLIPIDEMIA AND ACTIVITY OF INTERLEUKIN-1BETA AND INTERLEUKIN-6 IN TYPE 2 DIABETES MELLITUS

Objective:To determine the relationship between blood pressure (BP), lipid metabolism and levels of IL-1beta and IL-6 in patients with type 2 diabetes mellitus (T2DM).Design and method:A total of 96 patients with T2DM (mean age 52.74 ± 9.56, 38 women) and 20 healthy volunteers were examined. A systo