Differences In IL-6 Levels Research Articles

The Effect of Mesenchymal Stem Cell Wharton’s Jelly on Nuclear Factor Kappa Beta and Interleukin-10 Levels in Osteoarthritis Rat Model

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease in one or more joints characterized by changes in pathological structures such as cartilage, hypertrophy, and remodeling of the subchondral bone and secondary inflammation of the synovium membrane, causing changes in joint components such as cells, matrices, and molecular production. At the molecular level, an imbalance between catabolic and anabolic activities in joint cartilage results in OA. Nuclear factor kappa beta (NFκβ) is a cytokine that plays an important role in the signaling pathway of the pathogenesis of OA in causing an inflammatory reaction, whereas interleukin (IL)-10 is an anti-inflammatory cytokine that is involved in the pathogenesis of OA.
 AIM: This study aims to prove the influence before and after administration mesenchymal stem cells from Wharton’s jelly on the serum NFκβ and IL-10 levels in OA rat models.
 MATERIALS AND METHODS: This research is an experimental study with the design of post-test-only control group design. The sample consisted of 16 OA rats as a control group and 16 OA rats treated with MSC-WJ as a treatment group. OA induction is done by injection of monosodium iodoacetate (MIA) into the intra-articular right knee. Giving MSC-WJ is done in the 3rd week after MIA induction. The serum NFκβ and IL-10 levels were measured after 3 weeks treated with MSC-WJ using the ELISA method. The statistical test used is an independent t-test. p < 0.05 was said to be statistically significant.
 RESULTS: From the research results obtained, serum levels of knee OA of rat knee OA treated with mesenchymal stem cell Wharton jelly are lower than serum NFκβ levels of knee OA of the rat that is not treated, but the difference in levels of NFκβ is not significant (p > 0.05). The serum IL-10 level of rat OA of knee treated with mesenchymal stem cell Wharton jelly was higher than the serum IL-10 level of rat OA of the knee that was not treated, difference in levels of IL-10, is significant (p < 0.05).
 CONCLUSION: This study concluded that MSC-WJ significantly decreased the serum NFκβ levels of OA rats and not significantly increased the serum IL-10 levels of OA rats.

Interleukin 6 and Interleukin 10 in Patients Before and After Lung Transplantation

The aim of the study was to investigate the serum concentration of cytokines (interleukin 6 [IL-6] and IL-10) in patients before and after lung transplantation (LTx). The studied groups consisted of 14 patients (9 men and 5 women aged 47.7 ± 11.4; body mass index [BMI] 21.9 ± 2.3) followed for up to 6 months after LTx and 29 patients (15 men and 14 women, age 49.2 ± 9.4; BMI 23.1 ± 3.7) who were considered for LTx. The study population consisted of patients with idiopathic lung disease (ILD; 8 vs 17) and patients with chronic obstructive pulmonary disease (COPD; 6 vs 12). Cytokine serum levels were assessed using commercially available enzyme-linked immunosorbent assay kits. Significantly lower levels of IL-10 were observed in the group of patients considered for LTx compared to those in recipients (1.8 ± 0.99 vs 5.1 ± 1.44; P = .000726). Significantly lower levels of IL-10 were observed in the group of patients with ILD considered for LTx compared to recipients (1.8 ± 0.95 vs 3.4 ± 1.16; P = .005984). There were no differences in levels of IL-10 in the group of patients with COPD. There were no differences in levels of IL-6 when the studied groups were compared.The present results introduce the cytokines IL-6 and IL-10 in patients before and after LTx. The procedure of LTx influenced increasing of plasma concentration of IL-10. Immunosuppressive drugs may affect IL-10 serum levels. Further studies are needed to evaluate whether analyzed cytokines could be used as biomarkers of clinical status in patients before and after LTx.

Effectiveness of Soursop Leaf Extract (Annona muricata l.) on IL-6 Levels in Mammary Sprague dawley Female Rats Induced by Staphylococcus aureus

Staphylococcus aureus is a Gram-positive bacterium that causes inflammation such as mastitis in the breast. Breast mastitis can occur in nursing mothers and requires first aid or initial treatment. Herbal ingredients can be utilized because they are easily obtained and can be prepared by the community themselves. The study aimed to analyze the effectiveness of soursop leaf extract on IL-6 levels in mammae of female rats Sprague dawley induced by S. aureus. The study was divided into four groups consisting of five rats that were induced by S. aureus 2 x 107 CFU/ml. Group I was given 0.5% Na.CMC, Group II gave 45 mg/kgBW cefadroxil antibiotics, group III administered 100 mg / kgBW soursop leaf extract, and group IV administered soursop leaf extract combined with cefadroxil. Each group was given treatment twice a day for 5 days. IL-6 levels were measured on days 3 and 6. The results of this study showed IL-6 levels in group III were 7.50 ± 1.74 pg/ml on the 3rd day, and 4.51 ± 1.47 pg/ml on the 6th day. The results showed there were differences in IL-6 levels in group III (p = 0.037). Soursop leaf extract can be used as a therapy for mastitis caused by S. aureus.

Alterations of plasma cytokine biomarkers for identifying age at onset of schizophrenia with neurological soft signs

Several studies have been suggested that immunity plays a part in neurodevelopment and schizophrenia pathogenesis. Early age of onset in schizophrenia is associated with genetic factors which affect neurodevelopment. This study aims to identify immune abnormalities associated with neurodevelopmental impairments in early-onset schizophrenia (EOS) and adult-onset schizophrenia (AOS) patients. We determined the plasma levels of six cytokines (IL-1β, IL-4, IL-6, IL-10, IL-12 and TNF-α) in schizophrenia patients and healthy controls. Measurements included neurological soft signs (NSS) to distinguish and subgroup those with neurodevelopmental impairments. The study included 210 schizophrenia patients, which were divided into 84 EOS and 126 AOS patients, as well as 122 healthy controls. We observed significant differences in levels of IL-4, IL-6 and IL-10 between EOS and AOS patients. The results demonstrated the area under ROC curve (AUC) of the IL-4 in EOS and healthy controls was 0.81. Moreover, these results indicated that AUC of the IL-4 and the combination of IL-4, IL-6 and IL-12 in EOS with NSS and healthy controls were 0.91 and 0.95. These cytokines are altered in EOS and schizophrenia patients with neurodevelopmental impairments and demonstrated good classification abilities. These findings manifested that both pro- and anti-inflammatory cytokines are contributed to the clinical and pathophysiological features of schizophrenia. Future works are expected to explore potential genetic effectors and predictors as well as therapeutic directions in personalized medicine for early-onset schizophrenia.

Relationship between Angiogenic and Inflammatory Biomarkers and Diabetic Retinopathy

Background: Diabetic retinopathy (DR) is a common complication of diabetes mellitus and a major cause of vision loss in the working age population. Its pathogenesis is poorly understood but may involve low grade chronic inflammation and angiogenesis. The aim of this study was to evaluate the relationship between serum levels of one inflammatory (IL-6) and angiogenic cytokine (VEGF-A) with the presence and severity of DR in type 2 diabetic mellitus patients. Methods: From January to June 2019, we conducted a cross-sectional analytical study on 84 patients out of which 31 developed DR and 53 did not. All patients underwent complete ophthalmological examination and laboratory analysis for IL-6 and VEGF-A with ELISA Technique. We studied the relation of IL-6 and VEGF-A with the presence and severity of DR, HBA1c, the duration of diabetes. Results: The group with DR had statistically significant higher levels of VEGF-A compared to the control group (390.5 pg/ml vs. 173.1 pg/ml; p = 0.007). There was no significant difference in IL-6 levels between both groups (42.8 pg/ml vs. 31.7 pg/ml; p = 0.10). Equally there was no association between these 2 cytokines and macular oedema or with the severity of DR. The level of IL-6 was associated to the balance of diabetes (p = 0.006) although VEGF-A was not (p = 0.15). Moreover, Il-6 (p = 0.31) and VEGF-A (p = 0.24) were not linked to the duration of diabetes. Conclusion: Serum concentrations of VEGF-A have an effect on the development of DR. They correlate with the presence of the disease but IL-6 does not. However, IL-6 was associated to the balance of diabetes. These 2 biomarkers may play a role in the pathophysiology of diabetes and the diabetic retinopathy. Findings on Il-6 and VEGF-A may therefore contribute to the development of the diagnosis tools and caretaking of diabetes and diabetic retinopathy.

Influence of Intravenous Fish Oil-Enriched Lipid Emulsion on the Inflammatory Response in Children Post Gastrointestinal Surgery

Abstract: Background and Objective: Surgery can increase morbidity and mortality due to the production of proinflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Intravenous fish oil-enriched lipid emulsion (FOLE) contains ω-3, which can reduce the release of proinflammatory cytokines. The influence of FOLE compared to that of the standard medium chain triglyceride (MCT)/long chain triglyceride (LCT) emulsion on the inflammatory response in children post gastrointestinal surgery has never been studied. The current study was designed to explain the influence of FOLE on the inflammatory response in children post gastrointestinal surgery. Materials and Methods: A randomized controlled trial was conducted in August 2018-January 2019 at Dr. Soetomo Hospital in children post gastrointestinal surgery due to esophageal and intestinal atresia that requires parenteral nutrition for at least 3 days. The samples were divided randomly into MCT/LCT and FOLE groups. Laboratory and cytokine parameters were examined before and at 3 days after surgery. Results: Among all patients, 7/14 were male and 7/14 received FOLE. There were no significant differences in Hb, leukocyte, CRP, albumin, SGOT and SGPT levels in either group. The difference in IL-6 levels was significant between the two groups before surgery (p = 0.048), at 3 days after surgery (p = 0.013) and in changes within 3 days (p = 0.003). TNF-α levels were not significantly different compared to MCT/LCT at day 3 post surgery (p = 0.482). Conclusion: FOLE, compared to standard emulsions, can decrease IL-6 in postoperative children.

P4679Changes in systemic inflammation and endothelial dysfunction after balloon pulmonary angioplasty

Abstract Introduction Pulmonary endarterectomy leads to a decrease in systemic inflammation and improvement in endothelial function in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) improves pulmonary hemodynamics in patients with inoperable CTEPH. Aim To assess changes in systemic inflammation and endothelial dysfunction after a single BPA session and after completion of the treatment. Methods We enrolled consecutive, inoperable CTEPH patients who underwent BPA. Interleukin 6, 10 (IL-6, IL-10), and C-reactive protein (hsCRP) constituted markers of systemic inflammation. Endothelin-1 (ET-1) served as a marker of endothelial dysfunction. Serum concentration of selected markers was assessed in every patient before, 24 hours after the first BPA session and 6 months after completion of the BPA treatment. Age- and sex-matched healthy subjects served as a control group. Results We recruited 20 patients with inoperable CTEPH (6 males [30%]), aged 67 [61–74] years in New York Heart Association class III (n=19 [95%]) and II (n=1 [5%]). BPA treatment was completed with a median of 5 [2–8] BPA sessions per patient. Before starting the treatment CTEPH patients, as compared to controls (n=10), had raised serum level of IL-6 (3.82 [2.75 - 6.03] vs. 2.64 [0.88 - 4.75] pg/ml; p=0.04), hsCRP (2.47 [0.93 - 4.27] vs. 1.23 [0.48–3.21] ng/ml; p=0.02) and ET-1 (2.68 [2.24 - 3.64] vs. 1.47 [1.4 - 1.82] pg/ml; p=0.004). There was no difference in IL-10 level. 24 hours after a BPA session we observed an increased level of IL-6, IL-10 and hsCRP. (Tab.) 6 months after completion of the BPA treatment there was a reduced level of IL-6, hsCRP and ET-1 (Tab.) Table 1. Changes (Δ) in serum concentration of analyzed markers 24 hours after a single BPA session and at 6-months assessment after completion of the BPA treatment (n=20) Initial Δ at 24 hours after single BPA p Δ at 6-months follow-up p ET-1 [pg/ml] 2.68 [2.24; 3.64] −0.2 [−0.5; 0.23] 0.21 −0.47 [−0.96; 0.05] 0.004 IL-6 [pg/ml] 3.82 [2.75; 6.03] 3.67 [1.41; 7.16] 0.008 −0.82 [−3.11; 0.54] 0.04 IL-10 [pg/ml] 0.53 [0.44; 0.58] 0.32 [0.21; 0.87] 0.006 −0.11 [−0.33; 0.14] 0.94 hsCRP [ng/ml] 2.47 [0.93; 4.27] 5.4 [3.96; 10.59] 0.008 −0.36 [−0.94; 0.16] 0.02 ET-1, endothelin 1; hsCRP, C-reactive protein; IL-6, interleukin 6; IL-10, interleukin 10. Conclusions Patients with inoperable CTEPH, as compared to healthy controls, exhibit an increased systemic inflammation and endothelial dysfunction, which both improve after completion of the BPA treatment. At short-term follow-up after single BPA session there is an increase in systemic inflammatory response.

Effects of a Preoperative Transdermal Fentanyl Patch on Proinflammatory Cytokine and Pain Levels During the Postoperative Period: A Randomized Controlled Trial.

Objective:The main objectives of this article were to assess the effect of preoperative transdermal fentanyl patch (TFP) on interleukin (IL)-6 and IL-8 levels and pain after laparoscopic cholecystectomy.Materials and Methods:Patients received a TFP (25 μg/h) (patch group, n=30) or a placebo patch (control group, n=30) applied 14 hours before operation. After surgery, control group received intravenous continuous fentanyl (25 μg/h) with loading dose (25 μg). IL-6 and IL-8 levels were measured at admission and 1, 6, 12, 24, and 48 hours postoperatively. Pain score and consumption of rescue analgesic were evaluated too.Results:At 24 hours postoperatively, IL-6 and IL-8 reached a peak and then decreased. The peak IL-6 levels were 21.92(±6.22) and 24.91(±6.81) pg/mL in the patch and control group. The significant differences of IL-6 between groups were shown at 6 and 12 hours postoperatively (P=0.032, 0.0001). There were no significant differences in IL-8 levels and pain score.Conclusions:Preoperative TFP attenuated the increase in IL-6 levels after surgery and provided similar analgesia to continuous fentanyl infusion. Preemptive TFP may have influence on proinflammatory reactions and pain control after surgery.

Cytokine profile of cattle blood serum in the treatment of the hoof sole ulcers

The paper deals with the results of investigation inflammation markers level ‒ IL-1-RA (receptor antagonist IL-1), IL-4, IL-6 cows serum, patients with soles ulcers when performing orthopedic hoof treatment with two methods ‒ local treatment, and complex method ‒ local treatment in combination with the of epidural analgesia 0,2% bupivacaine. Therapeutic blockade with local anesthetics make analgesic and pathogenetic therapeutic effects on the animal organism, can be successfully used as a component of postoperative analgesia in surgical treatment. Bupivacaine ‒ local anesthetic can be used for epidural analgesia in the postoperative period with the blocking of sensory fibers without loss of motor function. It makes sense to study using of 0,2% bupivacaine solution in clinical conditions with a therapeutic purpose in surgical diseases of cattle. Determination of the level of interleukins is informative in relation to the study of the course of the inflammation process, the immune status of animals during treatment, and indicates the intensity of regenerative processes in damaged tissues. The purpose of the research is to determine the state of inflammatory response to the level of serum blood cytokines in cows with hoof sole ulcers for two treatment methods ‒ local in animals of the control group and integrated treatment in animals of the experimental group, which included local treatment with the therapeutic bupivacaine epidural blocks. In the control group of animals (n=5), only the local treatment. Animals of the experimental group (n=5), conducted an epidural puncture and catheterization between the last sacral and the first caudal vertebrae. The catheter was left in the epidural space. Bupivacaine injection was performed with an analgesic and therapeutic purpose of 0,2 % solution in terms 3 days. After the first injection of bupivacaine, the hoof sole was cleaned and treated locally. As inflammatory markers, the level of IL-1-RA (IL-1 receptor antagonist), IL-4, IL-6 in serum was studied, since the level of these indicators reflects the state of the pro- and anti-inflammatory system. In the course of the research, the obtained results of the control and experimental groups among themselves were compared, with the baseline data before treatment in each group, as well as with the indicators of clinically healthy cows. We conducted a comparative characteristic of indicators in the application of integrated treatment compared with only local treatment of the site of the lesion. Blood was taken from the tail vein. Stages of research: before orthopedic treatment, after orthopedic treatment in 30 minutes, 3 days, 14 days, 34 days after starting treatment. Blood serum tests were conducted in the Laboratory “Alvis-class”, Kharkiv using the semi-automatic immunoassay analyzer StatFax 303+ (USA). It was found that the use of a complex treatment method is accompanied by a lower level of inflammatory reaction of the body of cows compared with only local treatments. In animals of both groups, the level of IL-1RA significantly did not change throughout the study period, compared with the rates before treatment, but was significantly different in both groups of diseased animals (p <0,05 and p <0,01) from the indicator of healthy animals, which is associated with the presence of chronic inflammatory process ‒ hoof sole ulcers. The level of anti-inflammatory cytokine IL-4 in diseased animals prior to treatment did not differ from that of healthy animals. During treatment in animals in the experimental group, this indicator was significantly increased earlier than in the control group, compared with the baseline (p<0,05) and healthy animals (p<0,01), indicating a gradual activation of the anti-inflammatory cytokine and contributed to the tissues regeneration of affected limbs. However, such changes occurred later in the animals of the control group than in the animals of the experimental group. Dynamics of level IL-4 in animals with ulcerous soles is associated with the activation of recovery processes of damaged tissues, which in the experimental group manifested at earlier times than in the control. The content of IL-6 diseased animals, which is the main inducer of the acute phase of inflammation, was significantly higher in both animal groups prior to treatment than in healthy animals. In experimental animals in 3 days the level of IL-6 decreased by 5,3 times, in control ‒ by 3,3 times. After 14 and 34 days in both groups there was a further decrease in the level of IL-6. Considering that IL-6 is the main inducer of the acute phase of inflammation it can be difference in IL-6 level in the animals of the experimental and control groups was due to the effect of the therapeutic epidural blockade of bupivacaine, which increased blood circulation, trophic processes in the limb region, which contributed to accelerating the regeneration of damaged tissues. Key words: hoof sole ulcers, epidural analgesia, bupivacaine, interleukins, IL-1-RA, IL-4, IL-6, cattle.

Serum cytokine profile in schizophrenic patients.

Schizophrenia is a chronic severe mental disorder in which immunologic imbalances have been reported. Some researchers have demonstrated dysregulation of cytokine levels in this mental disorder. Considering the possible role of cytokines in the pathogenesis or clinical course of schizophrenia, we assessed serum levels of IL-4, IL-10, IL-17A and IFN-γ in a homogenous sample of Iranian patients who were in remission under treatment with Clozapine compared with sex and age matched controls. There was a statistically significant difference in IL-4 levels between patients and healthy subjects (P= 0.023). IL-4 levels were 83% higher in cases than in control group. No significant group*gender interaction was detected suggesting the similar IL-4 levels between males and females in each study group. There was no statistically significant difference in IFN-γ levels between patients and healthy subjects, but IFN-γ levels were 70% higher in male compared with female group. No significant differences have been found in serum levels of other cytokines between cases and controls or between males and females. The higher levels of IL-4 in patients treated with Clozapine might be due to effects of this antipsychotic drug on immune responses. Future studies are needed to elaborate the exact underlying mechanism.

Study on the immunity protection of 14-3-3–MPLA–liposome vaccine against cystic echinococcosis in mice

The study aims to investigate the protective immunity against Echinococcus granulosus in mice immunized with14-3-3–MPLA–liposome vaccine. ICR (Institute of Cancer Research) mice were subcutaneously immunized three times with 14-3-3–MPLA–liposome vaccine, followed by the challenge with Echinococcus granulosus protoscoleces intraperitoneally and then sacrificed after six months of post-challenge. The levels of IL-4, and IFN-γ were measured by ELISA. The rate of reduced hydatid cyst and the levels of IgE, IgG and IgG subclasses in sera were examined. The result showed that mice vaccinated with14-3-3–MPLA–liposome vaccine and challenged with protoscoleces revealed significant protective immunity of 95.07%. ELISA analysis indicated that the immunized mice generated specific high levels of IgG and the prevailing isotypes of IgG were IgG1 and IgG2a. The level of IFN-γ increased significantly in the vaccinated mice whereas there was no significant difference in IL-4 levels between vaccinated and control mice. It is concluded that the14-3-3–MPLA–liposome vaccine could induce a high level of protective immunity to prevent cystic echinococcosis. The MPLA and liposome are promising vaccine adjuvant and delivery system.

Microbiota Phylogenic Analysis Revealed Decreased Abundance of Faecalibacterium Prausnitzii, an Anti-Inflammatory Commensal Bacterium, in Patients with Chronic Graft-Versus-Host Disease

NF and RZG contributed equally to this workBackground: Preservation of intact gut microbiota (GM) in allogeneic hematopoietic stem cell transplant (alloHCT) recipients has gained intense attention over the last decade. Loss of GM diversity and a shift in GM composition after alloHCT has been associated with adverse consequences, including increased treatment related mortality due to acute graft-versus-host disease (GVHD), infection and organ failure. Despite a growing understanding of relationships among GM, systemic inflammation and acute GVHD in early stage (up to day 100) recovery, little is known about the GM alterations in late phase (beyond 100 days) recovery of alloHCT recipients with chronic GVHD (cGVHD). We compared the GM microbiota composition (diversity, richness and taxa abundance) and prototypical cytokines (IL10, anti-inflammatory and TNFα, pro-inflammatory) between alloHCT recipients with and without cGVHD in late phase HCT recovery. Method: This cross-sectional study included two groups of adults (age > 18 years) who received T cell repleted grafts and had a fecal and blood sample collected in late phase recovery of alloHCT. Group 1 (n=9) included patients with active moderate to severe cGVHD requiring systemic steroids +/- therapeutic dose Tacrolimus. Group 2 (n=11) included patients without cGVHD off Tacrolimus or on Tacrolimus taper (n=7: no cGVHD history and n=4: resolved cGVHD). Independent t-tests were used to examine clinical and transplant characteristics between groups. The V1-V3 region of the 16S rRNA gene in fecal specimens was sequenced using Illumina MiSeq. Sequenced data were processed using Quantitative Insights into Microbial Ecology (QIIME) version 1.9.1. Taxonomic assignment was done using ribosomal database project classifier with confidence cutoff set to 50%. Beta diversity analysis through Principal Coordinate Analysis (PCoA) was generated from UniFrac and Bray-Curtis distances. Difference in GM composition was tested using PERMANOVA. Alpha diversity analysis was done using Chao1 and Shannon diversity indices. Linear discriminant analysis effect size (LEfSe) was used to find markers that differentiate between groups. Cytokines were analyzed in plasma using Bioplex® multi-plex assay. Differences between groups were tested using Mann-Whitney U test. Correlations between cytokines and F. prausnitzii were tested using Spearman's Rho. Significance was set at < 0.05 for all tests. Results: No significant differences noted in characteristics of the two groups except for lower performance status in cGVHD (Table 1). There was a significant difference in GM composition between groups (Figure A, P = 0.002). Alpha diversity (richness) was significantly lower in setting of cGVHD (Figure B, p < 0.05). Based on LEfSe analysis, 13 GM taxa were associated with Group 1 and 48 taxa were associated with Group 2. The GM community in Group 1 was enriched with Bacteroides, Lactobacillus, Clostridium and Veillonella whereas GM of Group 2 was enriched with Ruminococcus, Blautia and Faecalibacterium (p <0.05 and LDA threshold value > 2). Interestingly, Faecalibacteriumprausnitzii (F. prausnitzii) was significantly enriched in group 2 (Figure C, p= 0.01). F. prausnitzii, a member of the Firmicutes phylum, is a well-known anti-inflammatory commensal bacterium. Previous studies have shown lower levels F. prausnitzii in patients with intestinal inflammatory diseases including active ulcerative colitis. Recently, F. prausnitzii has also been linked to response to anti-PD1 therapy. Differences in levels of IL10 and TNFα between groups were nearing significance (p=0.06 and p= 0.08, respectively). There was a significant correlation between IL10 level and F. prausnitzii (rho=0.55, p= 0.01) but not between TNFα and F. prausnitzii (rho= -0.35, p= 0.12). Conclusion: These data suggest patients with cGVHD have reduced GM diversity and distinct GM composition compared to patients without cGVHD. The finding of decreased abundance of F. prausnitzii, in patients with cGVHD offers insights into the mechanisms of inflammation in cGVHD and suggests a role for commensal bacteria-mediated anti-inflammatory activities in this population. Future studies are needed to better understand the immunomodulatory effects and potential therapeutic role of F.prausnitzii and GM composition in cGVHD to develop targeted interventions to improve outcomes of alloHCT recipients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Influence of Smoking on Gingival Crevicular Fluid Interleukin 1β and Interleukin-8 in Patients with Severe Chronic Periodontitis among a Rural Population in India.

Background and Objective:Smoking is widely prevalent among rural Indian populations. Smoking is considered a significant risk factor for periodontal diseases. The aim of the present study was to evaluate the influence of smoking on the inflammatory cytokines interleukin (IL) IL-1β and IL-8 in gingival crevicular fluid (GCF) and compare these between smokers and nonsmokers with periodontitis in diseased and healthy sites.Materials and Methods:A total of thirty patients with severe chronic periodontitis (15 smokers and 15 nonsmokers) participated in this study. Clinical parameters assessed were gingival index, bleeding on probing, probing depth (PD), and clinical attachment level. One diseased and one healthy site from each of the periodontitis patients were selected for GCF collection and assigned to the following four groups: healthy sites in smoker (SH), diseased sites in smoker (SD), healthy sites in nonsmoker (NH), and diseased sites in nonsmoker (ND) and were analyzed by enzyme-linked immunosorbent assay test (Quantikine®).Results:Intragroup comparisons revealed statistically significant levels of IL-1β in ND sites compared to NH sites (P < 0.005) and SD sites showed statistically significantly higher levels of IL-1β compared to SH sites (P < 0.0001). However, there was no significant difference in IL-8 levels between NH and ND sites as well as between SH and SD sites. Intergroup comparisons revealed that SH sites exhibited significantly lower amounts of IL-8 (P < 0.01) compared to NH sites and SD sites showed significantly lower levels of IL-8 compared to ND sites (P < 0.001). However, the comparison of NH and SH sites as well as ND and SD sites showed no significant difference in the levels of IL-1β.Conclusions:Cytokine levels were significantly elevated in periodontitis patients. Smokers exhibited a decrease in IL-8 and increase in IL-1β levels. Hence, this reflects the influence of smoking on immunosuppression and its role in the pathogenesis of periodontal disease.

Enhancement of Hepatitis E Virus DNA Vaccine Immunity by Beclin-1- Mediated Autophagy

Background: The Hepatitis E virus (HEV) infection is a serious public health problem, with a mortality rate of approximately 20-25% among pregnant women. DNA vaccination was reported to induce humoral and cellular immune responses in murine models; however, a major problem of the strategy is its limited potency. Methods: In this study, we have investigated whether Beclin1, as an autophagy-inducing based plasmid, can serve as an immunostimulatory agent and promote the HEV specific protective immunity of naked DNA vaccine encoding truncated ORF-2 (HEV239). Plasmids encoding HEV239 with or without Beclin1 were used for the BALB/c mice immunization. Results: The results demonstrated a significant increase microtubule-associated protein light chain-3 II (LC3 II) as a marker of autophagy in the HEK293 cell, which were transfected by pVITRO-Beclin1 plasmid. The immunological effects of adding Beclin1 to HEV239 ORF-2 DNA vaccines were associated with the induction of the antigen-specific lymphocyte proliferation and the Th1-type cytokine (gamma-interferon (IFN-γ)), while there were no differences in IL-4 levels between the groups. Examination of humoral immune responses in vaccinated mice represented that immunization with pVITRO-HEV239- Beclin1 notably increased serum level of IgG2a and total IgG against HEV in comparison to the HEV239 plasmid alone. Conclusions: The strong Th1 immune response induced by the Beclin1 suggest that induction of autophagy can be an efficient approach to enhance the immunogenicity of DNA vaccine. This promising procedure could be further exploited as a potential therapeutic vaccine candidate in future studies.

More inflammation but less brain-derived neurotrophic factor in antisocial personality disorder

Antisocial personality disorder (ASPD) is highly comorbid with substance use disorders (SUDs). We hypothesize that chronic neuroinflammation and the loss of neurotrophic factors prompts the pathogenesis of both disorders. We used ELISA to measure plasma levels of proinflammatory (tumor necrosis factor-α [TNF-α], C-reactive protein [CRP]) and anti-inflammatory factors (transforming growth factor-β1 [TGF-β1] and interleukin-10 [IL-10]), and brain-derived neurotrophic factor (BDNF) in male patients with ASPD (n=74), SUDs (n=168), ASPD comorbid with SUDs (ASPD+SUDs) (n=438), and Healthy Controls (HCs) (n=81). A multivariate analysis of covariance (MANCOVA) controlled for possible confounders was used to compare cytokines and BDNF levels between groups. The results of MANCOVA adjusted for age showed a significant (p<0.001) main effect of diagnosis on inflammatory factors and BDNF expression in these groups. ASPD, SUDs, and ASPD+SUDs patients had significantly (p<0.001) higher TNF-α levels but lower TGF-β1 and BDNF levels. SUDs and ASPD+SUDs patients had higher IL-10 levels than did ASPD patients and HCs. There was no difference in IL-10 levels between HCs and ASPD. Moreover, subgrouping SUDs and ASPD±SUDs into opioid use disorder (OUD) and other SUDs groups showed that the IL-10 levels were specifically higher in OUD and ASPD±OUD groups than other SUDs (P≤0.001). We conclude that uncontrolled inflammation and losing neurotrophic factors, with or without comorbid SUDs, underlies ASPD. IL-10 expression might be more specifically associated with OUD.

Abstract 212: Card9-mediated Signaling is Critical to Cytokine Production in Mice With PM Exposure

Oxidative stress and inflammation are considered an important mechanism for the development of cardiovascular diseases. Cytokines including interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) play an important role in oxidative stress and inflammation. It is known that ambient fine particulate matter ( PM ) exposure is closely associated with cardiovascular diseases and oxidative stress. Caspase-recruitment domain 9 ( Card9 ) signaling is critically involvement in the function of macrophages, neutrophils and monocytes that are important for oxidative stress and inflammation. The present study was designed to evaluate the role of CARD9-mediated signaling in cytokines production in mice with PM exposure. Both male wild-type (WT) C57BL/6 mice (8-10 weeks) and age-matched CARD9 knockout (KO) mice (with C57BL/6 background) were exposed to PM2.5 for 6 weeks via intranasal approach with PBS as the control. Serum concentrations of the cytokines including IL-6, IL-1β, and TNF-α were measured with ELISA in the mice before and after PM exposure. There was no difference in the serum levels of IL-6, IL-1β, or TNF-α between WT mice and CARD9 KO mice exposed to PBS. As expected, PM exposure substantially increased the serum levels of IL-6, IL-1β, and TNF-α in the WT mice (by up to 6 times). However, no significant increase in the serum concentrations for IL-6, IL-1β, and TNF-α was observed in CARD9 KO mice exposed to PM. Increased inflammatory infiltrations in the lungs were observed in the WT mice as compared to the CARD9 KO mice with PM exposure. In conclusion, the present study demonstrated that increased cytokines were produced in WT mice, but not in CARD9 KO mice with PM exposure. The data suggested that CARD9 signaling played a critical role in the production of inflammatory cytokines in the mice in response to PM exposure, and might contribute to the development of cardiovascular diseases related to PM exposure.

Serum tumour necrosis factor-α and interleukin-6 levels in Alzheimer's disease and mild cognitive impairment.

Neuroinflammation has been recognized as a feature of Alzheimer's disease (AD), and mild cognitive impairment (MCI) is believed to share several pathological features with AD. The aim of the present study was to compare serum cytokine levels between patients with AD, subjects with MCI, and healthy controls, and to assess the correlation between cytokine levels and cognitive performance in these subjects. Participants included 35 patients with AD, 29 subjects with MCI, and 28 healthy controls from the Department of Psychiatry of IIlsan Paik Hospital in South Korea. Demographic and neuropsychological information were obtained, and peripheral cytokine levels, specifically tumour necrosis factor (TNF)-α and interleukin (IL)-6 levels, were measured for all subjects. After adjustment for age, a significant difference in IL-6 levels (P = 0.045), but not in TNF-α (P = 0.082) levels, was observed among the three groups. IL-6 levels were higher in patients with AD than in subjects with MCI and healthy controls. TNF-α and IL-6 levels negatively and positively correlated with Mini-Mental State Examination and Global Deterioration Scale scores, respectively. TNF-α and IL-6 levels were also positively correlated with each other. The present study suggests that serum IL-6 levels of patients with AD might be higher than those of subjects with MCI and healthy controls. Serum TNF-α and IL-6 levels might be negatively correlated with cognitive function, and we suspect that serum IL-6 levels could be biomarkers for AD.

Morphine exposure during early life alters thermal and mechanical thresholds in rats

BackgroundMorphine is an opioid analgesic used to relieve moderate-to-severe pain, including pain in neonates at the intensive care unit. In our previous study, we showed that repeated morphine exposure during early life could trigger long-lasting implications on the developing nervous system, such as long-term neurochemical and behavioral alterations in adult rats. AimsThe aim of our study was to determine the short-, intermediate-, and long-term effects of repeated morphine administration during early life on the thermal and mechanical thresholds and on the central levels (cerebral cortex and brainstem) of neurotrophins (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]) and cytokines (interleukin-6 [IL-6] and IL-10). MethodsMale Wistar rats were administered morphine (5μg/day, s.c.) or saline for 7days from postnatal day 8 (P8) until P14. The nociceptive effect was assessed by evaluating the thermal response using the hot plate test (HPT) and the mechanical response by Von Frey (VFT) and Randall-Selitto (RST) tests at P16, P30, and P60. BDNF, NGF, IL-6, and IL-10 levels were measured in the cerebral cortex and brainstem. ResultsIn HPT, no difference in latency was observed at P16; however, at P30 and P60, the morphine-treated group exhibited a less increase in the nociceptive threshold compared to the saline group. VFT and RST demonstrated an interaction between group and age, where the morphine group showed a less pronounced increase in latency with age, which is indicative of allodynia. In the cerebral cortex, an association between BDNF and NGF levels and age was observed, where neurotrophin level increased with age in the saline group, and decreased with age in the morphine group. In addition, IL-10 levels decreased with age in both groups; however, there was no significant difference in IL-6 levels. In the brainstem, BDNF, NGF, IL-6, and IL-10 levels increased with age. DiscussionRepeated morphine exposure during neonatal life triggered alterations in the nociceptive behavior, including thermal hyperalgesia and mechanical allodynia, as well as decreased levels of BDNF and NGF in the cerebral cortex. Our study highlights the importance of extensive comprehension of the pharmacological interventions during CNS maturation.

Abstract # 1866 How is the immune balance affected in patients with generalised anxiety disorder?

Introduction Greater understanding of the role of cytokines in interactions between the nervous and immune systems has led to integrative and explanatory models for neuropsychiatric disorders. Our study aimed to examine peripheral inflammatory cytokines and immune balance in generalised anxiety disorder (GAD). Methods A case-controlled cross-sectional study investigated associations between psychological and biological variables. 54 patients with GAD and 64 healthy controls were recruited. Participants completed self-report measures of anxiety and depression. A panel of two pro-inflammatory and two anti-inflammatory cytokines were measured using multiplex technology. Results Case-control logistic regression analyses revealed significant differences in serum levels of IL-10, TNF- α , and IFN- γ between GAD and control groups after adjusting for age, gender and body mass index: these group differences were independent of the presence or degree of depression. Comparison of pro- and anti-inflammatory cytokine ratios indicated that there were significantly higher ratios of TNF- α /IL10, TNF- α /IL4, IFN- γ /IL10, and IFN- γ /IL4 in the GAD group compared to the control group. Conclusions This study is the first to investigate both pro- and anti-inflammatory cytokines and their balance in patients with GAD in comparison to healthy controls. The findings indicate a relatively increased pro-inflammatory response and diminished anti-inflammatory response and provide the first demonstration of a Th1/Th2 cytokine imbalance in GAD. The changes in serum cytokine levels in GAD were independent of the presence of depression.

Levels of CD40L and other inflammatory biomarkers in obese and non-obese women with polycystic ovary syndrome.

We investigated whether changes in sCD40L, hs-CRP, IL-6, and TNF-α levels are associated with polycystic ovary syndrome (PCOS). Case-control study involving 143 women with and 165 women without PCOS. Reduced sCD40L, and increased hs-CRP and IL-6, but not TNF-α, levels were seen between cases and controls. ROC analysis demonstrated high sensitivity and specificity for sCD40L and hs-CRP as PCOS predictors. Altered sCD40L levels were associated with PCOS, irrespective of body weight. Significant differences in IL-6 levels were seen between non-obese subjects and for TNF-α in obese subjects. sCD40L correlated negatively with age, insulin, HOMA-IR, LH, free testosterone, FAI, and hirsutism, but positively with SHBG. CRP correlated positively with BMI, insulin, HOMA-IR, free testosterone, and hirsutism. IL-6 correlated positively with hirsutism. TNF-α correlated positively with age, but negatively with insulin and HOMA-IR. CD40L, more than IL-6, or TNF-α, constitutes a predictor to explain PCOS and associated features.