Interlukin-10 Research Articles

Hepatoprotective and antioxidant effects of Octopus vulgaris extract against Depakine®-induced hepatotoxicity in adult rats

Background and objective Antiepileptic drug Depakine® is often used, although it can cause birth defects in both human and animals. This study’s goal was to assess the Octopus vulgaris extract’s (OE) ability to protect against the hepatotoxicity caused by Depakine in an effort to advance its clinical application. Patients and methods Four groups of adult male Wistar rats (150–180 g b.w.) have been designed at random (10 rats each) as: 1) healthy control group; 2) healthy rats treated orally with OE (50 mg/kg/day); 3) rats administrated orally with Depakine® (500 mg/kg/day); 4) rats treated with OE in combination with Depakine. Results and conclusion After 6 weeks of treatment, the results demonstrated that OE was effective in lowering Depakine®-induced hepatotoxicity. This was shown by a significant rise in liver glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) values as well as albumin and total protein levels. Additionally, there was a considerable drop in the serum levels of tumor necrosis alpha (TNF-α), interlukin-1beta (IL-1β), interlukin-4 (IL-4), interlukin-6 (IL-6), and interlukin-10 (IL-10), which exacerbated the structural recovery of the liver’s histological image. Conclusion: OE was highly effective in reducing the oxidative stress caused by Depakine® and protecting the liver from its toxic effects. OE is a viable supplement candidate for liver protection against the negative effects of that antiepileptic medication.

Comparison of Interlukin-10, Tumor Necrosis Factor-α and Complement-3 Levels among Bangladeshi Pregnant Women with or without Hepatitis E Virus Infection

Background: Several plasma proteins are proposed as biomarkers for acute HEV infected patients, but have not been validated among pregnant Bangladeshi women infected with HEV.
 Objective: In this present study, levels of interlukin-10 (IL-10), tumor necrosis factor α (TNF-α) and complement-3 (C3) were measured among HEV infected pregnant women and were compared with pregnant and HEV infected women.
 Methodology: This comparative cross-sectional study was conducted among the pregnant women who were admitted to the Department of Medicine, Department of Obstetrics & Gynecology, and Department of Hepatology of Dhaka Medical College Hospital (DMCH) and Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh for 1 year period. The study population included acute HEV infected pregnant women (HEV-P), healthy pregnant women (HPC) and HEV-infected non-pregnant women (HEV-NP) of the same age group. Interlukin-10 (IL-10), Tumor necrosis factor α (TNF-α) and complement 3(C3) levels were quantified by enzyme linked immunosorbent assay (ELISA) and turbidometry, respectively.
 Result: A total number of 81 women were recruited for this study of which 31 cases were acute HEV infected pregnant women (HEV-P); 25 cases were healthy pregnant women (HPC) and 25 cases were HEV infected non-pregnant women (HEV-NP) of the same age group. The mean levels with SD of the C3 level showed significant difference (P; 0.05) between groups of HEV-P (67.73±38.24 mg/dl), HEV-NP (147.9±22.28 mg/dl) and HPC (182.6±17.49 mg/dl). Though plasma TNF-α did not show any significant change (P; .05) in any of the groups, the IL-10 level was elevated significantly (p; 0.05) in HEV infected pregnant patients (0.187±0.3 ng/ml) then the non-pregnant HEV patients (0.027 + .08 ng/ml) and pregnant women group (0.012±0.04 ng/ml).
 Conclusion: In conclusion, increased levels of C3 and IL-10 observed in HEV infected pregnant women.
 Journal of National Institute of Neurosciences Bangladesh, July 2022;8(2):157-161

The role of mesenchymal stem cells in allergic rhinitis and its relationship with IL-10, plasma cells and regulatory T cells.

Aim Allergic rhinitis (AR) is an IgE-mediated inflammation of the nose. Regulatory T cells (Tregs), plasma cells and inflammatory cytokines have shown to play a critical role in allergic airway inflammation. The aim of the study was to investigate the role of mesenchymal stem cells (MSCs) in generating Treg cells and plasma cells associated with regulating interlukin-10 (IL-10) in AR model. Methods Fifteen male Wistar rats (6 to 8 weeks old) were randomly divided into three groups (control group, sham group, and MSCs treatment group). Ovalbumin (OVA) nasal challenge was conducted daily from day 15 to 21, and MSCs (1x106) were administrated intraperitoneally to OVA-sensitized rats on day 21. Sneezing was observed from day 24 to 27. The rats were sacrificed on day 24 and day 27. The expression of Treg and plasma cells was analysed by flow cytometry assay. The level of IL-10 was analysed under ELISA assay. Results This study showed that the percentage of sneezing and rubbing times significantly decreased in MSCs treatment associated with the regulation of IL-10 level and plasma cell. This finding was aligned with the significant increase of Treg level. Conclusion MSCs administration regulates IL-10 and plasma cell-mediated immune and inflammatory responses while increasing Treg cell production. MSCs may be a promising therapeutic target for treating Treg-mediated allergic diseases.

Protective Effect of Spirulina against Aspartame Induced Oxidative Stress and Molecular Gene Brain damage

Spirulina and lipoic acid has been considered as one of the most effective in ant oxidative stress and anti-inflammatory activity.Aspartame (ASP) is one of the mostwidely used (artificial sweeteners)used in a variety of foods and feeds.This study was conducted to evaluate the possible protective effect of Spirulina and alpha-lipoic acid against aspartame induced oxidative stress and brain damage in rabbits. Forty two white male New-Zealand Rabbits were classified into seven equal groups. Group I: (Control group) received no drugs. Group II: rabbits administered with aspartame (250 mg/kg b. wt/day). Group III: rabbits received alpha- lipoic acid (100 mg/kg b. wt/day). Group IV: rabbits received spirulina platensis (1500 mg/kg. b. wt/day). Group V: rabbits received aspartame (250 mg mg/kg b. wt) and treated with alpha- lipoic acid (100 mg/kg b. wt). Group VI: rabbits received aspartame (250 mg mg/kg b.wt) and treated with spirulina platensis (1500 mg/kg b. wt). Group VII: rabbits received aspartame (250 mg mg/kg b.wt) and treated daily with alpha- lipoic acid (100 mg/kg b. wt) and spirulina platensis (1500 mg/kg b. wt) for 8 weeks. At the end of experiment brain tissue were isolated and analyzed for determination of L-malondialdehyde (L-MDA), Catalase (CAT) and reduced glutathione (GSH) in addition to Anti-inflammatory cytokines: Interlukin-10 (IL-10),Activator Protein-1(AP-1),Bax gene expression and DNA damage. The obtained results showed a significant up-regulation of Activator Protein-1(AP-1),Bax gene expression level and a significant down-regulation of Interlukin-10 (IL-10) and marked increase in L-MDA and DNA damage that was indicated by an increase in tail length and tail DNA percent in brain tissue of aspartame treated rabbits. However, brain CAT activity andGSH concentration were markedly decreased when compared with control group.Coad ministration of spirulinaand alpha lipoic acid protect aspartame induced brain damage in rabbits caused a significant improvement of all previous parameters and attenuate DNA changes. Conclusively, spirulina platensis and alpha-lipoic acid exerts a protective effect against DNA damage and oxidative stress in brain of aspartameusage through free radical scavenging and anti-inflammatory activities as well as regenerating endogenous antioxidants defense system mechanisms.

Effect of Autologous platelet-rich plasma versus platelet-rich fibrin on the Second Intension Wound Healing in Dogs through higher regeneration capacity and modulation of inflammatory cytokines

Platelet rich plasma (PRP) and platelet rich fibrin (PRF) are considered excellent concentrated sources of growth factors (PDGF, TGF-β, VEGF, bFGF) and cytokines fundamental for wound healing. The aims of this study were to evaluate and compare the effect of PRP and PRF on the second intention wound healing through clinical vision, histopathological examination, and changes in the IL10 and TGF-β genes expression. Fifteen adult dogs were used in this study; induction of a 3cm diameter total thickness cutaneous injury at the right chest region. The animals were divided into three groups equally, and the wounds were treated twice weekly for three successive weeks. The first group (Group A) received only normal saline (control group). The second group was treated by PRP (group B). The third group received PRF treatment (group C). Clinical Evaluation, Molecular studies of interlukin 10 (IL10) and transforming growth factor-β (TGF-β) gene expression, and histopathological examination were used to demonstrate the difference between the three treatment regimens. Results showed a non-significant negative correlation between weight loss and WHR% and showed a significantly high positive correlation between treatment cost either by PRP or PRF with IL10 (0.79*) and WHR% (wound healing rate) (0.994**). The IL10 significantly increased in PRP group, while TGF-b was significantly increased in the PRF group. This study concluded that the PRP and PRF exhibited higher regeneration capacity and accelerates the quality of wound healing

Abstract 5096: The differences in immune composition observed between astrocytomas and oligodendrogliomas are due to genetics

Abstract We and others have shown that IDH-mutant astrocytomas and oligodendrogliomas share a common lineage hierarchy and a common cell of origin. However, IDH-mutant astrocytomas are infiltrated with immunosuppressive myeloid cells from the periphery to a degree not observed in IDH-mutant oligodendrogliomas. The abundance of blood-derived myeloid cells is prognostic in IDH-mutant glioma, and myeloid-derived suppressive cells are a barrier to emerging immunotherapies. Nonetheless, the cause of the differences observed between IDH-mutant subtypes is unknown. We performed single-cell RNA sequencing (scRNA-seq) and/or single-cell assay for transposon-accessible chromatin sequencing (scATAC-seq) on a cohort of 30 human primary IDH-mutant gliomas, including both astrocytomas and oligodendrogliomas. We integrated these single-cell multi-omics data to elucidate receptor-ligand interactions between tumor cells and myeloid cells, as well as the cis-regulatory grammars and associated transcription factors regulating these interactions. We validated these interactions in situ using imaging mass-cytometry on human specimens. We identified macrophage colony-stimulating factor (CSF1) and other genes responsible for myeloid cell chemotaxis, interlukin 10 (IL10), transforming growth factor beta (TGFB1) and genes responsible for promoting aberrant myeloid activation, as differentially expressed and showing differential chromatin accessibility between astrocytomas and oligodendrogliomas. The promoters of these genes were enriched for STAT3, SOX2, and SOX17/OCT4 recognition motifs, which were also differentially enriched between astrocytomas and oligodendrogliomas in our scATAC-seq data and differentially expressed in our scRNA-seq data. Since the scATAC-seq peaks in these genes correlated with known binding sites of the chromatin-modifying enzyme ATRX, and since ATRX possesses loss-of-function mutations in over %80 of IDH-mutant astrocytomas but almost never in oligodendrogliomas, we hypothesize that the observed differences in myeloid abundance are driven by a loss of ATRX binding in key chemotactic and immunosuppressive cytokines and their upstream transcription factors. To test this hypothesis, we knocked out ATRX in a a syngeneic, immunocompetent glioma mouse model using CRISPR and profiled the resulting tumors via a battery of genomics and protein-level assays. We conclude that the differences in immune composition between IDH-mutant glioma subtypes are due to genetics. In particular, ATRX loss of function in IDH-mutant astrocytoma leads to chromatin changes in STAT3 and downstream effector cytokines, resulting in a greater influx of immunosuppressive myeloid cells. Citation Format: Lin Wang, Husam Babikir, Karin Shamardani, Francisca Catalan, Aaron Diaz. The differences in immune composition observed between astrocytomas and oligodendrogliomas are due to genetics [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5096.

Management of Citrus sinensis peels for protection and treatment against gastric ulcer induced by ethanol in rats

Introduction: Stomach ulcer is one of the most prevalent disorders worldwide. The study was aimed to isolate and characterize the major polymethoxylated flavonoids in Citrus sinensis peels petroleum ether extract and investigate its protective and curative effect on gastric ulcer.Material and methods: Some spectral analyses were used for identification of the isolated compounds from the petroleum ether extract of Citrus sinensis peels. One oral dose (0.5 ml/100 g b.wt.) of absolute ethanol was orally given to rats after starvation for 24 h to induce gastric ulcer. To explore the protective and curative role of the plant extract, it was orally (250 mg/kg b.wt.) given for 1 week either before or post-ulcer induction. A reference drug, ranitidine (100 mg/kg b.wt.), was also evaluated. Stomach acidity, gastric volume, lesion counts, glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), acid phosphatase (AP), interlukin-10 (IL-10) and prostaglandin E2 (PGE2) were estimated. Stomach histopathological features were monitored.Results: Nine polymethoxy flavonoids were identified from the extract. Treatment with C. sinensis peels extract recorded amelioration in all parameters.Conclusion: Citrus sinensis petroleum ether peels extract had protective and curative effects against gastric ulcer. Therefore, the extract recorded anti-secretory, anti-ulcerative, anti-inflammatory, and antioxidant effects. Its healing action exceeded its protective role due to its richness in polymethoxylated flavonoids

Relation of Epstein Barr virus with interleukin-10 Levelamongmen with Prostate Cancer in Ramadi City

The study aimed at evaluating the relation of Epstein Barr virus (EBV)with level of interlukin-10 (IL-10) in men withprostatecancer(PC). The study was carried out in Ramadi city from 12th of January to 12th of September 2018, and included a total of 95 women withbreast cancerwho admitted to oncology clinic ofRamadi Teaching Hospital whose ages were between 40-80 years. Patients were investigated for detection of EBV by using Real Time PCR and interleukin-10 (IL-10) by ELISA technique.The rate of prostate cancer men with EBV was (16.84%). The highest rate of prostate cancer menwas within the age group 50-59 years with no significant relation between prostate cancer and age. The study showed that the highest means of IL10 level (19.43 pg/ml) were found in prostate cancer men without EBV.There was significant difference (P value<0.05) between EBV infection with IL-10. The highest rate of men withprostate cancer was fromurban areas.

A Novel wx2 Gene of Toxoplasma gondii Inhibits the Parasitic Invasion and Proliferation in vitro and Attenuates Virulence in vivo via Immune Response Modulation.

Toxoplasma gondii (T. gondii) is an obligate intracellular apicomplexan protozoan that can parasitize most warm-blooded animals and cause severe diseases in immunocompromised individuals or fetal abnormalities in pregnant woman. The treatment of toxoplamosis has been limited by effective drugs. Our previous work indicated that the novel gene wx2 of T. gondii may serve as a vaccine antigen candidate. To further investigate the molecular functions of wx2 in highly virulent T. gondii (RH strain), a wx2 gene deletion mutant RH strain (KO-wx2) was established using CRISPR-Cas9. The phynotype of KO-wx2 was analyzed by plaque, invasion, and replication assays in vitro as well as in vivo virulence assays. The results indicated that the targeted deletion of the wx2 gene significantly inhibited in vitro parasite growth and replication in the host cells as well as attenuated parasite virulence in the mouse model. Notably, the percentage of pro-inflammatory factors of interferon gamma (IFN-γ) and interlukin-17A (IL-17A) and anti-inflammatory factor of interlukin-10 (IL-10) in the lymph nodes were upregulated in mice infected with the KO-wx2 strain. Our data suggested that the wx2 gene plays an important role in the process of the parasite’s life cycle and virulence in mice. In addition, it also plays an important role in the host’s immunity reaction, mainly via Th1 and Th17 cellular immunity, not Th2.

Neuroprotective effect of Costus afer on low dose heavy metal mixture (lead, cadmium and mercury) induced neurotoxicity via antioxidant, anti-inflammatory activities

Humans are constantly exposed to heavy metals due to their ubiquity in the environment. Hence, this study investigated the possible protective effect of Costus afer aqueous leaf extract (CALE) against low dose heavy metal mixture (LDHMM)-induced neurotoxicity. Male albino rats were divided into 6 equal groups. Group 1 served as the normal control receiving only deionized water. Group 2 served as the toxic control receiving on metal mixture (20 mg/kg PbCl2, 1.61 mg/kg CdCl2 and 0.40 mg/kg HgCl2), groups 3, 4 and 5 were co-treated with metal mixture and CALE (750, 1500 and 2250 mg/kg body weight, respectively) and group 6 was treated with metal mixture and ZnCl2. All treatments were administered through oral gavage for 90days. Oxidative stress biomarkers [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione content (GSH) and catalase (CAT)], inflammatory cytokines [interlukin-6 (IL-6) and interlukin-10 (IL-10)], histopathological changes and heavy metal concentration were determined in brain of rats. Results indicated that LDHMM significantly increased (p < 0.05) the lipid peroxidation marker (MDA) and the pro-inflammatory cytokine (IL-6), while lowered levels of the oxidative biomarkers (SOD, CAT and GSH) and anti-inflammatory cytokine (IL-10). Also, LDHMM caused some histopathological changes such as reactive gliosis and glia cell proliferation. LDHMM elevated the lead, cadmium and mercury concentrations in the brain. Severity of the distorted cortical parameters were ameliorated by CALE administration. The CALE induced significant protective effect on LDHMM-mediated neurotoxicity in a dose-dependent manner which may be a result of its antioxidant anti-inflammatory and metal chelation mechanisms.

Effect of a synbiotic supplement on cecal microbial ecology, antioxidant status, and immune response of broiler chickens reared under heat stress

The aim of this study was to examine the effect of a dietary synbiotic supplement on the cecal microflora, antioxidant status, and immune response of broiler chickens under heat stress (HS). A total of 360 one-day-old male Ross 708 broiler chicks were randomly distributed among 3 dietary treatments containing a synbiotic (PoultryStar consists of Bifidobacterium animalis, Enterococcus faecium, Lactobacillus reuteri, Pediococcus acidilactici, and fructooligosaccharides) at 0 (control), 0.5 (0.5X), and 1.0 (1.0X) g/kg. Each treatment contained 8 replicates of 15 birds each housed in floor pens. Heat stimulation was at 32°C for 9h daily from day 15 to 42. Heat stress-induced changes of cecal bacteria were detected using bacteria-specific agars, and spleen protein concentration and mRNA expression of interleukins and antioxidants were examined using ELISA and real-time PCR, respectively. Under the HS condition, synbiotic fed broilers regardless of dose had lower cecal enumerations of Escherichia coli and coliforms, and a lower heterophil/lymphocyte (H/L) ratio (P < 0.05) compared to controls. 1.0X group also had higher cecal enumerations of Bifidobacterium spp. and Lactobacillus spp., spleen glutathione peroxidase (GPx), and plasma nuclear factor erythroid 2-related factor 2 (Nrf-2), and a lower H/L ratio compared to both control and 0.5X groups (P < 0.05). However, there were no treatment effects on the levels of Enterococcus spp., the circulating monocytes, eosinophils, and basophils, Toll like receptor-4 (TLR-4), interleukin-6 (IL-6), interlukin-10 (IL-10), and their mRNA expression, as well as plasma Kelch-like ECH-associated protein 1 (Keap-1) (P > 0.05). These results suggest that the synbiotic could inhibit the negative effects of HS on broiler health through the reduction of cecal pathogens, regulation of stress reactions, and improvement of antioxidant status.

Male infertility and viral infection: Interference role of the human herpesvirus types (3 – 6) with disturbances effects of some cytokines hypersecretion and seminal oxidative defense system in the infertility etiopathogenesis of some idiopathic infertile Iraqi patients

To study the role of potential relationship of chronic human herpes virus types (3 – 6) infection and their correlation with the up-regulation of some cytokines (IL-2, IL-10 and IFN gamma) and effect of (8-OHdG) and (TAOC) levels onto male infertility. A Case – control study with semen samples which were collected by masturbation during the routine semen analysis of a total ninety age-matched participants as; fertile males 35 (38.9%) with proven fertility as a normal semen quality and infertile males 55 (61.1%) with at least one year of infertility and poor semen quality. All semen biomarkers of Human herpes viruses (HHVs): Varicella zoster virus (VZV-IgG), Epstein-Barr virus (EBV-IgG), Cytomegalovirus (CMV-IgG), Human herpes virus type 6 (HHV6-IgG), Interlukin-2 (IL-2), Interlukin-10 (IL-10), Interferon-gamma (IFN-γ), 8-hydroxy-2'-deoxy guanosine (8-OHdG) and Total Antioxidant Capacity (TAOC) which were included in the study had been estimated by quantitative ELISA based method and the correlations with sperms parameters were evaluated. The main significant outcomes in this study of the infertile males group 55 (61.1%) were: high percentages of seminal IgG; N (%; Mean±SD) were detected of HHV6, 48 (53.3%;1.26± 0.51) then CMV, 39 (43.3%;1.51± 0.95) followed by EBV, 34 (37.8%; 2.20±1.47), and the highest abnormal cytokines levels were estimated in; 44 (48.9%; 112.62±38.64) and 40 (44.4%; 22.75±10.65) for IFN-γ and IL-10 respectively. Furthermore, High 8-OHdG level was detected in 47 (52.2%;7.29±2.15) and very low level of TAOC was detected in 16 (17.8%;19.34±12.17). Significant negative correlation between semen biomarkers and standard sperms parameters was found which were represented by: 45 (50.0%) of total sperms count less than (33 million ml), 52 (57.8%) of progressive motile sperms less than (31%). Finally, about 33 (24.4%) of abnormal sperm morphology was detected. Our results hypothesized that chronic asymptomatic viral infection with increasing of cytokines concentrations consequently disturbance the semen oxidative status, antioxidant defense systems that induce sperms DNA damage then might be collectively act as a co-factors on the etiology of the male infertility.

Pulicaria crispa mitigates gastric ulcer induced by ethanol in rats: role of treatment and auto healing

Context: Stomach ulcers are the common gastrointestinal disorders worldwide. Objective: This study aimed to investigate the therapeutic impact of Pulicaria crispa aerial parts ethanol extract against gastric ulcer in rats. Materials and methods: Ulcer was induced by one oral dose of ethanol (0.5 ml/100g body weight) on 24 hours empty stomach, then the plant extract (500 mg/kg b.wt.) was orally administered daily for one week. Ranitidine (100 mg/kg b.wt.); as a reference drug was evaluated. Stomach acidity and volume, as well as lesion counts were measured. Levels of malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) were estimated. Assay of different marker enzymes; succinate dehydrogenase (SDH), lactate dehydrogenase (LDH), glucose-6-phosphatase (G-6-Pase), acid phosphatase (AP) and 5′-nucleotidase (5′NT) were determined. Interlukin-10 (IL-10), intracellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor alpha (TNF-α) were also determined. Stomach histopathological assessment was detected. Results: Gastric ulcer showed drastic changes in oxidative stress, cell organelles and inflammatory markers. These biomarkers served as good tools to identify the presence of gastric ulcer. Treatment with P. crispa recorded amelioration in most parameters exceeding the auto healing effect. Conclusion: Healing potency of P. crispa is possibly related to its content of glycosides, coumarins, flavonoids, tannins, sterols and triterpenes.

Genetic Polymorphisms and Cytokine Profile of Different Ethnicities inSeptic Shock Patients and their Association with Mortality.

ABSTRACTObjectiveThe outcomes of sepsis and septic shock patients are heterogonous, with avariable response despite standardized care. The aim of this study was toexplore the racial differences in septic shock outcomes, and theirassociation with genetic polymorphisms and cytokine levels in an Asianpopulation.Materials and methodsThis was an observational cohort study with Intensive Care units of a 500bedded tertiary care hospital in Singapore. 198 patients (73 Chinese, 73Malay and 52 Indian and others) admitted to the Khoo Teck Puat HospitalIntensive Care Unit between August 2016 and June 2017, with a diagnosis ofsevere sepsis (according to) were enrolled. Plasma interlukin-6 (IL-6),interlukin-10 (IL-10) and tumour necrosis factor-a (TNFa) were measuredusing a highly sensitive quantitative sandwich enzyme-linked immunosorbentassay (ELISA) (BioVendor, Modrice, Czech Republic). The gene panel studiedincluded 16 genes.ResultsThe rs7038903 common variant in SVEP1 gene showed significant associationwith sepsis severity independent of other variants in ordinal logistic andlinear regression model (p = 0.001 and p = 0.002 respectively). Moreover, the association between rs7038903 and increased hazard for death remained significant after further adjusting for cytokines level. Interestingly, significant differences were seen in plasma IL6 inindividuals with or without rs7038903 C allele (28pg/ml (IQR 12-86) vs90pg/ml (IQR 49-155); P=0.022) in patients with severe sepsis in the Malayethnic group.ConclusionOur study shows a promising polymorphism in SVEP1 gene (rs7038903) which isassociated with sepsis shock and 28 days mortality, independent of age, gender, and method of diagnosis and SOFA score. Collectively, while our findings so far have shown the additional value or measuring cytokines andgenetic markers in sepsis outcomes in the local population, further largescare studies are needed in a heterogeneous septic population with arigorous analysis to know the significance of our findings.How to cite this articleSiddiqui S, Gurung RL et al. Genetic Polymorphisms and Cytokine Profile of Different Ethnicities in Septic Shock Patients, and their Association with Mortality. Indian J Crit Care Med 2019;29(3):135-138.

1034P - A prospective multicenter study of primary breast lymphoma in the rituximab era: Prognostic implication of beta 2 microglobulin and interlukin-6 & interlukin-10

Background: Primary breast diffuse large B-cell lymphoma (DLBCL) is a rare entity representing ≤ 2% of extra-nodal non-Hodgkin lymphoma. We aimed to define clinical profile, prognostic factors and the incidence of the central nervous system (CNS) relapse in the era of rituximab and clarify the prognostic value of beta2 microglobulin(B2M), interlukins-6 (IL-6) and interlukin -10(IL-10). Methods: Between Jan 2012 to Dec 2016, a prospective analysis of 28 patients presenting to 7 academic Egyptian centers. All patients were females. Only patients with newly diagnosed stage I and II disease DLBCL were included. Patients with evidence of baseline CNS disease and patients with hepatitis B and HIV were excluded. All patients were scheduled to receive R-CHOP protocol plus involved- field radiotherapy. The prognostic significance of B2M, and IL-6 and 10 were assessed. Results: About 75% presented with breast mass, 4 cases with inflammatory symptoms, 3 cases were discovered by mammography. Right breast was more involved (64%), 86% had ≤ 1 ECOG performance status, and LDH elevated was in 39% and 18% had B symptoms. HCV was positive in 32% (9 patients). Stage I was detected in 57%. The stage–modified International prognostic index was ≤1 in 54%. Ten cases underwent breast surgery (2 modified radical mastectomy, 8 conservative breast surgery). Complete response was achieved in 23/28 (82%) with median follow-up of 28 months, 39% of patients had relapsed, contralateral breast was the site of initial relapse in two cases, 11% developed CNS relapse and 21% in other nodal and extranodal sites. Three years disease free survival and overall survival were 68% and 79%. Favorable prognostic factors according to univariate analysis were stage I, IPI≤1, tumor size < 5cm, B2M. IL6 and IL-10, while for multivariate analysis they were IPI≤1 and B2 M and IL-6. Conclusions: Primary breast DLBCL has high rate of CNS relapse in spite of era of rituximab so CT or MRI of CNS is necessary during follow-up. Prophylaxis to CNS should be considered in the initial treatment to improve outcome. In addition, assessment of pretreatment serum levels of B2M, and IL-6 in newly diagnosed DLBCL may indicate a possible prognostic role. Legal entity responsible for the study: Lobna Ezz el-arab. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Progranulin Is Positively Associated with Intervertebral Disc Degeneration by Interaction with IL-10 and IL-17 Through TNF Pathways.

Progranulin (PGRN) is a widely expressed growth factor that effectively inhibits tumor necrosis factor α (TNFα)-mediated inflammatory response. TNFα is involved in intervertebral disc degeneration (IDD) and plays a key role. This study aims to determine the role of PGRN in the intervertebral disc degeneration process. We collected intervertebral discs (IVDs) from humans and mice with different genetic backgrounds. We examined the expression of PGRN in IVD tissues by immunohistochemistry staining and Western blotting assay. We examined the peripheral serum level of PGRN by ELISA assay. Murine IVD tissue samples were taken to undergo safranin O, HE, and immunohistochemistry staining. Primary human nucleus pulposus cells were used for ELISA and RT-PCR assays. PGRN as well as interlukin-10 (IL-10) and interlukin-17 (IL-17) expressions were elevated in degenerative discs and peripheral blood sera. Loss of PGRN led to accelerated disc degeneration in the animal model, along with decreased expression of IL-10 and increased expression of IL-17. Additionally, the PGRN level was positively related to levels of IL-10 and IL-17. In vitro study suggested that PGRN protected against disc degeneration by inducing IL-10 and reducing IL-17. PGRN is associated with intervertebral disc degeneration through interfering with IL-10 and IL-17; thus, PGRN could be an interesting biomarker for diagnosis and a potential treatment target.

Effect of β-Glucans in Diets on Growth, Survival, Digestive Enzyme Activity, and Immune System and Intestinal Barrier Gene Expression for Tropical Gar (Atractosteus tropicus) Juveniles

The application of β-1,3/1,6-glucan derived from yeast at five concentrations (0%, 0.5%, 1.0%, 1.5%, and 2.0%) in formulated diets was evaluated in juveniles for its effects on the growth, survival, digestive enzymatic activity, and expression of genes associated with the immune system (interlukin-10 (IL-10), transforming growth factor (TGF), occludin (OCC), mucin2 (MUC2), lysozyme (LYS), and nucleotide-binding and oligomerization domain 2 (NOD2)) in tropical gar (Atractosteus tropicus). For the experiment, three replicates of 30 fish per experimental unit (70 L) were cultivated for 62 days. The growth results showed no statistically significant differences in relation to weight and total length between treatments. The activity of digestive enzymes (alkaline proteases, trypsin, leucine aminopeptidase, and amylase) did not show significant differences between treatments, except for chymotrypsin activity, where fish fed 1.0% and 1.5% of β-glucans showed higher activities compared with the rest of the treatments. On the other hand, the analysis of gene expression did not show significant differences between treatments, although a tendency of increase in the expression of IL-10, TGF, MUC2, and OCC was observed with an addition of 1.5% of the prebiotic, but there was a decrease in the fish fed with 2% of the prebiotic. It is possible to include concentrations of between 0.5% and 1.5% of β-glucans in the diets for A. tropicus, with no detectable adverse effects on growth, survival, digestive enzyme activity, or specific gene expression. β-glucan 1,3/1,6 added at 1.0% and 1.5% in the diet significantly increases chymotrypsin activity.

IL-10-1082 A&amp;gt;G (rs1800896) polymorphism confers susceptibility to pulmonary tuberculosis in Caucasians but not in Asians and Africans: a meta-analysis

Background: Earlier studies have shown that interlukin-10 (IL-10) -1082 A>G gene polymorphism is implicated in susceptibility to pulmonary tuberculosis (PTB), but their results are inconsistent and inconclusive. In the present study, a meta-analysis was performed to analyze the potential association between IL-10 -1082 A>G gene polymorphism and PTB susceptibility.Methods: A quantitative synthesis was done using PubMed (Medline), EMBASE, and Google Scholar web databases search and meta-analysis was performed by calculating pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for all the genetic models.Results: A total of 22 eligible studies comprising 4956 PTB cases and 6428 healthy controls were included in the analysis. We did not observe any increased or decreased risk of PTB in allelic contrast (G vs. A: P=0.985; OR = 1.001, 95% CI = 0.863–1.162), homozygous (GG vs. AA: P=0.889; OR = 1.029, 95% CI = 0.692–1.529), heterozygous (GA vs. AA: P=0.244; OR = 0.906, 95% CI = 0.767–1.070), dominant (GG + AG vs. AA: P=0.357; OR = 1.196, 95% CI = 0.817–1.752), and recessive (GG vs. AA + AG: P=0.364; OR = 0.921, 95% CI = 0.771–1.100) genetic models. Likewise, no association of IL-10 -1082 A>G polymorphism with PTB risk was observed in Asian and African population for all the genetic models. Interestingly, the dominant model (GG + AG vs. AA: P=0.004; OR = 1.694, 95% CI = 1.183–2.425) demonstrated increased risk of PTB in Caucasian population.Conclusions: This meta-analysis concludes that IL-10 -1082 A>G gene polymorphism is not significantly associated with overall, Asian and African population. However, this polymorphism is associated with Caucasian population.

An agent-based model of leukocyte transendothelial migration during atherogenesis.

A vast amount of work has been dedicated to the effects of hemodynamics and cytokines on leukocyte adhesion and trans-endothelial migration (TEM) and subsequent accumulation of leukocyte-derived foam cells in the artery wall. However, a comprehensive mechanobiological model to capture these spatiotemporal events and predict the growth and remodeling of an atherosclerotic artery is still lacking. Here, we present a multiscale model of leukocyte TEM and plaque evolution in the left anterior descending (LAD) coronary artery. The approach integrates cellular behaviors via agent-based modeling (ABM) and hemodynamic effects via computational fluid dynamics (CFD). In this computational framework, the ABM implements the diffusion kinetics of key biological proteins, namely Low Density Lipoprotein (LDL), Tissue Necrosis Factor alpha (TNF-α), Interlukin-10 (IL-10) and Interlukin-1 beta (IL-1β), to predict chemotactic driven leukocyte migration into and within the artery wall. The ABM also considers wall shear stress (WSS) dependent leukocyte TEM and compensatory arterial remodeling obeying Glagov’s phenomenon. Interestingly, using fully developed steady blood flow does not result in a representative number of leukocyte TEM as compared to pulsatile flow, whereas passing WSS at peak systole of the pulsatile flow waveform does. Moreover, using the model, we have found leukocyte TEM increases monotonically with decreases in luminal volume. At critical plaque shapes the WSS changes rapidly resulting in sudden increases in leukocyte TEM suggesting lumen volumes that will give rise to rapid plaque growth rates if left untreated. Overall this multi-scale and multi-physics approach appropriately captures and integrates the spatiotemporal events occurring at the cellular level in order to predict leukocyte transmigration and plaque evolution.

Interleukin-10 reorganizes the cytoskeleton of mature dendritic cells leading to their impaired biophysical properties and motilities.

Interlukin-10 (IL-10) is an immunomodulatory cytokine which predominantly induces immune-tolerance. It has been also identified as a major cytokine in the tumor microenvironment that markedly mediates tumor immune escape. Previous studies on the roles of IL-10 in tumor immunosuppression mainly focus on its biochemical effects. But the effects of IL-10 on the biophysical characteristics of immune cells are ill-defined. Dendritic cells (DCs) are the most potent antigen-presenting cells and play a key role in the anti-tumor immune response. IL-10 can affect the immune regulatory functions of DCs in various ways. In this study, we aim to explore the effects of IL-10 on the biophysical functions of mature DCs (mDCs). mDCs were treated with different concentrations of IL-10 and their biophysical characteristics were identified. The results showed that the biophysical properties of mDCs, including electrophoresis mobility, osmotic fragility and deformability, as well as their motilities, were impaired by IL-10. Meanwhile, the cytoskeleton (F-actin) of mDCs was reorganized by IL-10. IL-10 caused the alternations in the expressions of fasin1 and profilin1 as well as the phosphorylation of cofilin1 in a concentration-dependent fashion. Moreover, Fourier transformed infrared resonance data showed that IL-10 made the status of gene transcription and metabolic turnover of mDCs more active. These results demonstrate a new aspect of IL-10’s actions on the immune system and represent one of the mechanisms for immune escape of tumors. It may provide a valuable clue to optimize and improve the efficiency of DC-based immunotherapy against cancer.