IL-1 Alpha Research Articles

Serum resistin levels and resistin gene polymorphism in patients with acne vulgaris: does it correlate with disease severity?

Acne vulgaris is a disease that inflames the sebaceous gland with multiple etiologies. Many proinflammatory adipokines contribute to this pathogenesis. Resistin is a proinflammatory mediator that activates kappa B, a nuclear factor, and c-Jun N-terminal kinases pathways inducing toll-like receptor-2, interleukin-1, 6, and tumor necrosis factor alpha. Resistin gene affects the promoter and intron regions' polymorphisms' expression levels. We aimed to study the association of resistin gene polymorphisms (RETN -420 C/G) and the development of acne vulgaris and whether it is associated with serum resistin levels and disease severity. Resistin (RETN) gene (rs1862513) genotypes were identified using restriction fragment length polymorphism (RFLP), and serum resistin presence was assessed by enzyme-linked immunosorbent assay in 40 patients with acne vulgaris and 40 age- and sex-matched healthy controls as a cross-reference. Patients were divided into mild, moderate, and severe groups. Global Acne Grading System (GAGS) was used to assess the severity of acne vulgaris. CG and GG genotypes were present in cases (P = 0.006) odds ratio (OR)1 = 4.43; 95% confidence interval (CI) (1.53, 12.7) and OR2 = 5.47; 95% CI (0.99, 30.1); G-allele statistically dominated in the patient group where P = 0.001 and OR = 3.57; 95% CI (1.63, 7.80). A positive significant relationship between RETN genotypes and serum resistin levels and GAGS score was present. RETN genes rs1862513 GG and G allele are correlated to acne vulgaris development and severity in a sample of the Egyptian population. This study comprised a small sample size. The cases may not accurately represent the general population; only one clinic was enrolled in the study.

IL-1α and colorectal cancer pathogenesis: Enthralling candidate for anti-cancer therapy.

Inflammation has been well-established as a hallmark of colorectal cancer (CRC). Interleukin-1 alpha (IL-1α) is one of the primary inflammatory mediators driving the pathogenesis of inflammation-associated CRC. This systematic review presents the roles of IL-1α in the pathogenesis of the disease. Bibliographic databases PubMed, Science Direct, Scopus and Web of Science were systematically searched for articles that addresses the relationship between IL-1α and colorectal cancer. We highlighted various mechanisms by which IL-1α promotes the pathogenesis of CRC including enhancement of angiogenesis, metastasis, resistance to therapy, and inhibition of tumour suppressive genes. We also discussed the potential mechanisms by which IL-1α expression is induced or secreted in various studies. Beyond these, the systematic review also highlights several potential therapeutic strategies which should be further explored in the future; to target IL-1α and/or its associated pathways; paving our way in finding effective treatments for CRC patients.

Evaluation of the In vivo Antitumor Activity of Polyanhydride IL-1α Nanoparticles.

Cytokine therapy is a promising immunotherapeutic strategy that can produce robust antitumor immune responses in cancer patients. The proinflammatory cytokine interleukin-1 alpha (IL-1α) has been evaluated as an anticancer agent in several preclinical and clinical studies. However, dose-limiting toxicities, including flu-like symptoms and hypotension, have dampened the enthusiasm for this therapeutic strategy. Polyanhydride nanoparticle (NP)-based delivery of IL-1α would represent an effective approach in this context since this may allow for a slow and controlled release of IL-1α systemically while reducing toxic side effects. Here an analysis of the antitumor activity of IL-1α-loaded polyanhydride NPs in a head and neck squamous cell carcinoma (HNSCC) syngeneic mouse model is described. Murine oropharyngeal epithelial cells stably expressing HPV16 E6/E7 together with hRAS and luciferase (mEERL) cells were injected subcutaneously into the right flank of C57BL/6J mice. Once tumors reached 3-4 mm in any direction, a 1.5% IL-1a - loaded 20:80 1,8-bis(p-carboxyphenoxy)-3,6-dioxaoctane:1,6-bis(p-carboxyphenoxy)hexane (CPTEG: CPH) nanoparticle (IL-1α-NP) formulation was administered to mice intraperitoneally. Tumor size and body weight were continuously measured until tumor size or weight loss reached euthanasia criteria. Blood samples were taken to evaluate antitumor immune responses by submandibular venipuncture, and inflammatory cytokines were measured through cytokine multiplex assays. Tumor and inguinal lymph nodes were resected and homogenized into a single-cell suspension to analyze various immune cells through multicolor flow cytometry. These standard methods will allow investigators to study the antitumor immune response and potential mechanism of immunostimulatory NPs and other immunotherapy agents for cancer treatment.

Prognostic significance of cachexia in advanced non-small cell lung cancer patients treated with pembrolizumab.

Cancer cachexia is a multifactorial syndrome characterized by weight loss leading to immune dysfunction that is commonly observed in patients with advanced non-small cell lung cancer (NSCLC). We examined the impact of cachexia on the prognosis of patients with advanced NSCLC receiving pembrolizumab and evaluated whether the pathogenesis of cancer cachexia affects the clinical outcome. Consecutive patients with advanced NSCLC treated with pembrolizumab were retrospectively enrolled in the study. Serum levels of pro-inflammatory cytokines and appetite-related hormones, which are related to the pathogenesis of cancer cachexia, were analyzed. Cancer cachexia was defined as (1) a body weight loss > 5% over the past 6months, or (2) a body weight loss > 2% in patients with a body mass index < 20kg/m2. A total of 133 patients were enrolled. Patients with cachexia accounted for 35.3%. No significant difference in the objective response rate was seen between the cachexia and non-cachexia group (29.8% vs. 34.9%, P = 0.550), but the median progression-free survival (PFS) and overall survival (OS) periods were significantly shorter in the cachexia group than in the non-cachexia group (PFS: 4.2months vs. 7.1months, P = 0.04, and OS: 10.0months vs. 26.6months, P = 0.03). The serum TNF-alpha, IL-1 alpha, IL-8, IL-10, and leptin levels were significantly associated with the presence of cachexia, but not with the PFS or OS. The presence of cachexia was significantly associated with poor prognosis in advanced NSCLC patients receiving pembrolizumab, not with the response to pembrolizumab.

Entelon® (Vitis vinifera Seed Extract) Prevents Cancer Metastasis via the Downregulation of Interleukin-1 Alpha in Triple-Negative Breast Cancer Cells.

Interleukin-1 (IL1) is a proinflammatory cytokine and promotes cancer cell proliferation and invasiveness in a diversity of cancers, such as breast and colon cancer. Here, we focused on the pharmacological effect of Entelon® (ETL) on the tumorigenesis of triple-negative breast cancer (TNBC) cells by IL1-alpha (IL1A). IL1A enhanced the cell growth and invasiveness of TNBC cells. We observed that abnormal IL1A induction is related with the poor prognosis of TNBC patients. IL1A also increased a variety of chemokines such as CCL2 and IL8. Interestingly, IL1A expression was reduced by the ETL treatment. Here, we found that ETL significantly decreased the MEK/ERK signaling pathway in TNBC cells. IL1A expression was reduced by UO126. Lastly, we studied the effect of ETL on the metastatic potential of TNBC cells. Our results showed that ETL significantly reduced the lung metastasis of TNBC cells. Our results showed that IL1A expression was regulated by the MEK/ERK- and PI3K/AKT-dependent pathway. Taken together, ETL inhibited the MEK/ERK and PI3K/AKT signaling pathway and suppressing the lung metastasis of TNBC cells through downregulation of IL1A. Therefore, we propose the possibility of ETL as an effective adjuvant for treating TNBC.

MO413EFFECTS OF CHRONIC, LONG-TERM ACE-INHIBITOR TREATMENT ON CYTOKINE STORM AND RENAL FUNCTION AFTER CARDIO-PULMONARY BYPASS: A PROSPECTIVE OBSERVATIONAL STUDY

Abstract Background and Aims Cardiopulmonary bypass (CPB) may trigger organs damage, including kidney injury, due to a massive cytokine release. In this observational, prospective study, we have analyzed the possible impact of chronic treatment with ACE-Inhibitors (ACE-I) on the inflammatory response and renal function after CPB. Method Sixty-nine patients undergoing major cardiac surgery with CPB were enrolled. Patients were stratified according to long-term (&amp;gt;6 mo.) ACE-I use (n=38) or not (n=31). The primary endpoint was to analyze the changes in their IL-1 alpha, IL-1beta, IL-2, IL-4, IL-6, IL-8, IL-10, TNF alpha, EGF and VEGF plasma levels. Secondary (renal) endpoints were: postoperative acute kidney injury (AKI), recovery of baseline GFR values and the absolute changes in renal function indexes. Results After CPB, IL-1alpha, IL-1beta, IL-4 and TNF-alpha remained stable overtime, while a significant decrease in IL-2 plasma levels was noticed in the ACE-I group (p=0.01). IL-6 and IL-8 plasma levels increased after surgery and tended to decrease after 48h. IL-10 plasma levels showed a similar variation, but both their rise and decrease were more pronounced in patients under ACE-I treatment (p=0.007). Finally, VEGF and EGF showed a marked initial decrease with a tendency to normalization 10 days after surgery (p for trend ranging from 0.01 to 0.001) (Figure 1-2). The occurrence of AKI within 2 days after surgery, the rate of GFR recovery and the absolute changes in renal function indexes were not statistically different between groups (Figure 3). Conclusion Chronic, long-term ACE-I treatment may influence the inflammatory response following CPB. On the other hand, this drug class apparently has neutral impact on perioperative renal outcomes.

The role of single nucleotide polymorphisms of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) on susceptibility to herniated nucleus pulposus.

Background: The objective of this study was to determine the role of single nucleotide polymorphisms (SNPs) in interleukin 1 alpha ( IL-1A), tumor necrosis factor-alpha ( TNF-A), and vitamin D receptor ( VDR) genes on the susceptibility to herniated nucleus pulposus (HNP). Methods: Four databases (PubMed, Embase, Cochrane, and Web of Science) were searched as of April 1 st, 2021. Authors, publication year, targeted genes, genotype and allele frequency in each case and control groups were collected. Newcastle-Ottawa scale was used to evaluate the publication quality. The pooled estimates of association of IL-1A -889C>T (rs1800587), TNF-A -238G>A (rs361525), and VDR TaqI (rs731236) and susceptibility to HNP were assessed using Z test and presented as odd ratio (OR) and 95% confidence intervals (95%CI). Results: We screened 3,067 unique studies for eligibility and three, two and nine studies on IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI were included, respectively, in our meta-analysis. The studies consisting 369 HNP cases and 433 controls for IL-1A -889C>T, 252 cases and 259 controls for TNF-A -238G>A and 1130 cases and 2096 controls for VDR TaqI. Our pooled estimates indicated that there was no significant association of those SNPs with the susceptibility to HNP in any genotype, dominant model, recessive model, or allele comparations. Conclusion: Although individual studies suggested the important role of gene expression dysregulation associated with SNPs in IL-1A, TNF-A, and VDR, our data indicated that IL-1A -889C>T, TNF-A -238G>A, and VDR TaqI had weak association with HNP susceptibility in both genotypes and allele distributions. However, since heterogeneity was identified among studies included in this meta-analysis, further meta-analysis with a larger population and subgroup analysis on specific population are warranted to support this finding.

Genetic Predictors of Early-Onset Spinal Intervertebral Disc Degeneration: Part One of Two

Intervertebral disc (IVD) degeneration is a progressive and painful pathology that can root from mechanical, biochemical, and environmental stressors. However, recent advancements in biogenetics have now found a predominating genetic influence. Nevertheless, despite these advancements, the pathophysiology of IVD degeneration remains poorly understood. In the first of our two-part series, we will characterize some of the most recent and best-studied genes in the context of intervertebral disc degeneration. We will attempt to formulate the first contemporary gene guide that characterizes the genetic profile of IVD degeneration. The genes of interest include aggrecan (ACAN), matrix metalloproteinase 2 (MMP2), vitamin D receptor (VDR), interleukin 1 alpha (IL1A), and those encoded for collagens such as collagen type XI alpha 1 chain (COL11A1), collagen type I alpha 1 chain (COL1A1), collagen type IX alpha 2 chain (COL9A2), and collagen type IX alpha 3 chain (COL9A3). Genetic analysis studies reveal that these genes play vital roles in maintaining the structural integrity of the intervertebral disc, activating enzymes involved in the extracellular matrix, and promoting connective tissue formation. Nevertheless, characterizing these genes alone is not enough to understand the pathophysiology of IVD degeneration. Therefore, further studies are warranted to understand molecular signalling pathways of IVD degeneration better and ultimately create more sophisticated genetic and cell-based therapies to improve patient outcomes.

The Relationship between Inflammatory Cytokines and Coagulopathy in Patients with COVID-19.

Coronavirus disease 2019 (COVID-19), with a broad range of clinical and laboratory findings, is currently the most prevalent medical challenge worldwide. In this disease, hypercoagulability and hyperinflammation, two common features, are accompanied by a higher rate of morbidity and mortality. We assessed the association between baseline inflammatory cytokine levels and coagulopathy and disease outcome in COVID-19. One hundred and thirty-seven consecutive patients hospitalized with COVID-19 were selected for the study. Baseline interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha (TNF-α) level were measured at time of admission. At the same time, baseline coagulation parameters were also assessed during the patient’s hospitalization. Clinical findings, including development of thrombosis and clinical outcome, were recorded prospectively. Out of 136 patients, 87 (~64%) had increased cytokine levels (one or more cytokines) or abnormal coagulation parameters. Among them, 58 (~67%) had only increased inflammatory cytokines, 12 (~14%) had only coagulation abnormalities, and 17 (19.5%) had concomitant abnormalities in both systems. It seems that a high level of inflammatory cytokines at admission points to an increased risk of developing coagulopathy, thrombotic events, even death, over the course of COVID-19. Early measurement of these cytokines, and timely co-administration of anti-inflammatories with anticoagulants could decrease thrombotic events and related fatal consequences.

Association between interleukin-1 alpha rs1800587 polymorphism and rheumatoid arthritis: A meta-analysis.

No consistent results have been reached on the relationship of interleukin-1 (IL-1) rs1800587 polymorphism with the susceptibility to rheumatoid arthritis (RA) so far. Therefore, the current meta-analysis was designed to thoroughly review relevant studies, in order to examine the relationship of IL-1A rs1800587 polymorphism with RA risk. Electronic databases were retrieved for literature regarding the relationship between IL-1A rs1800587 polymorphism and RA vulnerability according to the inclusion and exclusion criteria. Stata 12.0 software was adopted to examine the enrolled literature. Meanwhile, odds ratio (OR) and corresponding 95% confidence intervals (95% CI) were used to evaluate the association. A total of seven case-control researches (3267 patients and 2960 healthy controls) were eventually enrolled into the current meta-analysis. Our data indicated no correlation of IL-1A rs1800587 polymorphism with RA risk (TT vs CC: OR = 0.90, 95% CI = 0.73-1.11; TC vs CC: OR = 1.02, 95% CI = 0.78-1.34; Dominant model: OR = 1.04, 95% CI = 0.80-1.35; Recessive model: OR = 1.91, 95% CI = 0.74-1.12). Similarly, no association was found in subgroup analysis stratified by ethnicity. Our findings indicated no relationship between IL-1A rs1800587 polymorphism and RA vulnerability.

High mortality co-infections of COVID-19 patients: mucormycosis and other fungal infections.

Severe COVID-19 disease is associated with an increase in pro-inflammatory markers, such as IL-1, IL-6, and tumor necrosis alpha, less CD4 interferon-gamma expression, and fewer CD4 and CD8 cells, which increase the susceptibility to bacterial and fungal infections. One such opportunistic fungal infection is mucormycosis. Initially, it was debated whether a person taking immunosuppressants, such as corticosteroids, and monoclonal antibodies will be at higher risk for COVID-19 or whether the immunosuppresive state would cause a more severe COVID-19 disease. However, immunosuppressants are currently continued unless the patients are at greater risk of severe COVID-19 infection or are on high-dose corticosteroids therapy. As understood so far, COVID-19 infection may induce significant and persistent lymphopenia, which in turn increases the risk of opportunistic infections. It is also noted that 85% of the COVID-19 patients’ laboratory findings showed lymphopenia. This means that patients with severe COVID-19 have markedly lower absolute number of T lymphocytes, CD4+T and CD8+ T cells and, since the lymphocytes play a major role in maintaining the immune homeostasis, the patients with COVID-19 are highly susceptible to fungal co-infections. This report is intended to raise awareness of the importance of early detection and treatment of mucormycosis and other fungal diseases, such as candidiasis, SARS-CoV-2-associated pulmonary aspergillosis, pneumocystis pneumonia and cryptococcal disease, in COVID-19 patients, to reduce the risk of mortality.

Hypoxia-Induced Reactivity of Tumor-Associated Astrocytes Affects Glioma Cell Properties.

Glioblastoma is characterized by extensive necrotic areas with surrounding hypoxia. The cancer cell response to hypoxia in these areas is well-described; it involves a metabolic shift and an increase in stem cell-like characteristics. Less is known about the hypoxic response of tumor-associated astrocytes, a major component of the glioma tumor microenvironment. Here, we used primary human astrocytes and a genetically engineered glioma mouse model to investigate the response of this stromal cell type to hypoxia. We found that astrocytes became reactive in response to intermediate and severe hypoxia, similarly to irradiated and temozolomide-treated astrocytes. Hypoxic astrocytes displayed a potent hypoxia response that appeared to be driven primarily by hypoxia-inducible factor 2-alpha (HIF-2α). This response involved the activation of classical HIF target genes and the increased production of hypoxia-associated cytokines such as TGF-β1, IL-3, angiogenin, VEGF-A, and IL-1 alpha. In vivo, astrocytes were present in proximity to perinecrotic areas surrounding HIF-2α expressing cells, suggesting that hypoxic astrocytes contribute to the glioma microenvironment. Extracellular matrix derived from hypoxic astrocytes increased the proliferation and drug efflux capability of glioma cells. Together, our findings suggest that hypoxic astrocytes are implicated in tumor growth and potentially stemness maintenance by remodeling the tumor microenvironment.

The revisited role of interleukin-1 alpha and beta in autoimmune and inflammatory disorders and in comorbidities.

The interleukin (IL) 1 family of cytokines is noteworthy to have pleiotropic functions in inflammation and acquired immunity. Over the last decades, several progresses have been made in understanding the function and regulation of the prototypical inflammatory cytokine (IL-1) in human diseases. IL-1α and IL-1β deregulated signaling causes devastating diseases manifested by severe acute or chronic inflammation. In this review, we examine and compare the key aspects of IL-1α and IL-1β biology and regulation and discuss their importance in the initiation and maintenance of inflammation that underlie the pathology of many human diseases. We also report the current and ongoing inhibitors of IL-1 signaling, targeting IL-1α, IL-1β, their receptor or other molecular compounds as effective strategies to prevent or treat the onset and progression of various inflammatory disorders.

The Apoptotic and Inflammatory Response of Brain Striatal Tissue to Extracorporeal Membrane Oxygenation (ECMO) Following the Model of Cardiac Arrest in Young Piglets

We investigated the effects of ECMO on pro-apoptotic and pro-inflammatory signaling in the striatum of piglets following cardiac arrest. 3-week-old piglets were anesthetized, paralyzed and ventilated. Oxygen in the ventilated gas was decreased from 21% to 7% - 10% over 30 min, then ventilation stopped until cardiac arrest. Three minutes after arrest, resuscitation began in two groups, without ECMO (CA) and with ECMO (ECMO). In a control group (C), the animals were sham operated. After 6 hours of recovery, the piglets were euthanized and stratum harvested. Measurement of apoptotic and inflammatory proteins was performed by RayBiotech, Inc. The results are means (6) ± SEM. There were no differences between CA and ECMO groups for anti-apoptotic proteins. ECMO significantly decreased pro-apoptotic proteins (Bax, cytoC, IGFBP-6, TNF-beta and TRAIR 1 and 3) as compared to CA group. Bcl-2 to Bax ratio increased in ECMO group suggesting that ECMO can least partially protect striatum from apoptotic injury. With respect to inflammation, ECMO significantly decreased both anti-inflammatory (ANG-1, FGF-21, IFN-alpha and beta, IGF-2, IL-10, IL-13, IL-1ra, IL-22, IL-4, IL-6, NCAM-1, SCF, TGF-alpha, TIMP-1and 2, VECF) and pro-inflammatory proteins (IL-12p40, IL-21, IL-15, IL-1 alpha and beta, IL-8, MIP-1 beta, OPG, PIGF-2, RANTES and TGF beta) in striatum of piglets. Conclusions: In a piglet model of cardiac arrest, ECMO significantly reduced levels of pro-apoptotic proteins without changing the levels of anti-apoptotic proteins. ECMO also significantly decreased the levels of both pro- and anti-inflammatory proteins. This decrease in the levels of both pro- and anti-inflammatory proteins may lead to disturbed neuronal metabolism and amplify inflammatory cell death.

Aberrant expression of proatherogenic cytokines and growth factors in human umbilical vein endothelial cells from newborns of type 2 diabetic women

Objectives:This study reports the levels of cytokines, chemokines, and growth factors previously identified as taking part in the pathology of atherosclerosis in human umbilical vein endothelial cells derived from mothers with type 2 diabetes and compares them with those in human umbilical vein endothelial cells derived from healthy mothers under normal glucose conditions.Methods:Cytokine analysis measures of human umbilical vein endothelial cell lysates were obtained using a multiple analyte profiling (xMAP) assay based on magnetic bead-based technology, using the MAGPIX instrument. The correlation between cytokines, chemokines, and growth factors was examined statistically in human umbilical vein endothelial cells derived from mothers with type 2 diabetes.Results:This study showed that the expression of proinflammatory cytokine interleukin-1 alpha was significantly greater in human umbilical vein endothelial cells derived from mothers with type 2 diabetes than those derived from healthy mothers. The protein level of granulocyte colony-stimulating factor was higher in human umbilical vein endothelial cells derived from mothers with type 2 diabetes than those derived from healthy mothers. A significant positive correlation was demonstrated between the protein expression of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in human umbilical vein endothelial cells derived from mothers with type 2 diabetes.Conclusion:Diabetes evokes a persistent inflammatory phenotype in human umbilical vein endothelial cells, as indicated by the enhanced production of cytokines and growth factors under normal glucose conditions.

Regulation of Cytokine and Growth Factor Gene Expression in Human Bone Marrow Stromal Cells Transformed With Simian Virus 40

Marrow stromal cells are thought to regulate hematopoiesis by producing colony-stimulating factors (CSFs) and other cytokines, either constitutively or in response to mediators such as interleukin-1 alpha (IL-1 alpha) or tumor necrosis factor-alpha (TNF alpha). The mechanisms by which these inflammatory cytokines induce CSF expression in stromal cells are not fully defined. In this study, we used human marrow stromal cells transformed by simian virus 40 (SV-MSCs) to study growth factor and cytokine gene regulation in response to IL-1 alpha and TNF alpha. IL-1 alpha induced significant and prolonged increases in steady-state mRNA levels for interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), granulocyte-macrophage CSF (GM-CSF), and, to a lesser extent, granulocyte-CSF (G-CSF); this induction was not dependent on new protein synthesis. Nuclear run-on analyses showed that IL-1 alpha transcriptionally activated the genes for IL-6, GM-CSF, and IL-1 beta, while TNF alpha transcriptionally induced expression of IL-6 and IL-1 beta. Furthermore, mRNA for IL-6 and IL-1 beta was dramatically superinduced by the combination of cycloheximide and TNF alpha. When SV-MSCs were cultured in semisolid medium, they formed colonies of blast-like cells that, when replated on plastic, resumed adherent growth. These "colony-derived" cell lines, unlike the parental SV-MSCs from which they were derived, constitutively expressed colony-stimulating activity and mRNA for GM-CSF, G-CSF, IL-6, and IL-1 beta. In this report, we show that the expression of IL-6 and IL-1 beta mRNA in the colony-derived cell lines was due, at least in part, to constitutive transcriptional activation of these genes (similar to the findings in IL-1 alpha- and/or TNF alpha-stimulated parental SV-MSCs). However, in contrast to the transcriptional activation of the GM-CSF gene seen in cytokine-induced parental SV-MSCs, GM-CSF transcripts accumulated in the colony-derived cell lines by a posttranscriptional mechanism.

Increased Serum IL 6 Associated With Mortality and Cognitive Impairment in Elderly Brazilians

Immunological and inflammatory changes are gaining importance in aging as they are associated with functional limitations and mortality. Chronic inflammation associated with aging (Inflammaging) is a systemic and subclinical condition, characterized by changes in the levels of interleukins such as IL1, IL4, IL6, IL8, IL10 and TNF alpha, associated with genetic, physiological and environmental factors, whose importance is to be directly associated with morbidity and mortality in the elderly. Objective: To evaluate, through a longitudinal study, the relationship between chronic inflammation associated with aging and possible outcomes, such as cognitive changes and mortality in independent oldest old adults. Methods: were evaluated 201 elderly, aged 80 years or older, community residents, with preserved cognition, without acute diseases and with controlled chronic diseases. In a 02 years of interval, laboratory collections of inflammatory markers (IL 1, IL 4, IL6, IL10, TNF alpha and CRP) were performed and outcomes such as cognitive impairment and deaths were evaluated. Results: There was a correlation between increased serum IL6 and cognitive impairment, in the group of women (p-value = 0.008) and in the group All (p-value = 0.022). In the group of men, there was a significant difference between the increase in IL6 values ​​(p-value = 0.028) and CRP (p-value = 0.016) in relation to deaths. Conclusion: The results of this longitudinal study showed and confirmed the positive association between changes in inflammatory markers such as IL6 and outcomes such as cognitive impairment and mortality also in elderly Brazilians.

Role of Innate Immunity in Patients with HBV Infection

Background: The hepatitis B virus [HBV] is an infectious disease and its one of the great public health problem, its outcome depends on the kinetics of the virus-host interaction and specifically on the strength of the innate and adaptive, humoral and cellular immune response. Thus interactions between the virus and the components of immune systems plays an important role in the pathogenesis of the disease. This study aimed to evaluate innate immune response in different clinical courses of HBV infection by estimation serum levels of granulocytemacrophagecolony stimulating factor (GM-CSF), Interleukin-1 (IL-1 ), Interleukin-8 (IL-8 ) , immunoglobulin A (IgA), IgM, IgG and Complement component (C3and C4) levels. Aim of study: to evaluate role of immune response in clinical course of hepatitis B infection Patients and Method: This study based on 78 patients with HBV infection attending the Public Health Laboratories. Their ages ranged from (14-65) years, (58 males and 20 females) compared with 20 healthy subjects (12 males and 8 females) as control group. This study extended from first of January 2015 to first of January 2017. The patients were classified to three groups on the bases of serologic markers (HBsAg, HBe Ag, HBc Ab IgM) according to WHO department of communicable disease surveillances and response, liver function tests which are used as supportive indicator for the liver injury, history of the illness, and full clinical assessment. The first group includes twenty-eight patients with acute HBV infection, second group include twenty cases identified as chronic healthy HBsAg carriers group and the last third group include thirty cases of chronic HBV group Results: By using enzyme immuno assay [ELISA] technique, serum levels of interleukin1alpha [IL-1α], interleukin-8 [IL-8], and granulocyte-macrophage-colony stimulating factor [GM-CSF] were measured in all patients compared to that of healthy control group. The mean levels of IL-1α and IL-8 showed a significant increase in serum of patients with newly infected (acute) HBV and chronic HBV compared with studied control group [P=0.04 and P=0.001 respectivel]. However, the mean serum levels for IL-1α and IL-8 recorded a non significant increase in patients with chronic healthy HBsAg carriers [P=0.17 and P=0.4 respectively]. While the mean serum levels of GM-CSF showed a significant rise in acute HBV only [P=0.01]. Moreover, serum immunoglobulins [IgG, IgM, IgA] and complement component [C3, C4] levels also evaluated by using single radial immunodiffusion test (SRID). The mean serum IgA, IgG and IgM levels showed a significant increase in chronic HBV group as compared to that of control group [ P=0.000 ,P=0.000 and P=0.001 respectively].. The mean serum C3 and C4 levels showed a significant lower serum level in all groups compared to control studied group [P=0.000]. Conclusion: this data demonstrate that immunological differences do exist between different clinical groups with HBV infection and may reflect the role of the innate immune system in host defense and disease

The Association between TNF-alpha, IL-1 alpha and IL-10 with Alzheimer's Disease.

Sporadic Alzheimer's Disease (AD) is assumed to be associated with different biological/genetic vulnerability, as well as with neuroinflammation, mediated by cytokines. The present study evaluated the role of cytokines in AD. The aim was to determine the possible association of TNF-α (rs1800629), IL1-α (rs1800587) and IL-10 (rs1800896) polymorphisms with AD, and to assess serum TNF-α, IL-1α and IL-10 concentrations in patients with AD and in subjects with mild cognitive impairment (MCI). The study included 645 Caucasian participants: 395 subjects with AD and 250 subjects with MCI. Genotyping was performed using real-time PCR in all 645 subjects, while serum concentrations of TNF-α, IL-1α and IL-10 and were determined using ELISA in 174 subjects. The frequency of the TNF-α rs1800629, IL1-α rs1800587 or IL-10 rs1800896 genotypes did not differ significantly between patients with AD and MCI. Serum concentration of IL-1α and IL-10 were significantly decreased, while the concentration of TNF-α was significantly higher in patients with AD than in MCI subjects. TNF-α, IL1-α or IL-10 concentrations were similar in subjects with AD or MCI subdivided into carriers of the corresponding TNF-α rs1800629, IL1-α rs1800587 or IL-10 rs1800896 genotypes. Similar distribution of the IL1-α rs1800587, TNF-α rs1800629 or IL-10 rs1800896 genotypes in subjects with AD and MCI failed to confirm that these specific risk genotypes are associated with vulnerability to develop AD. Alteration in IL-1α, IL-10 and TNF-α concentrations in patients with AD partially confirmed the association with the neuroinflammatory response in AD.

Efficacy and safety of rilonacept for recurrent pericarditis: results from a phase II clinical trial

ObjectiveRecurrent pericarditis (RP) incurs significant morbidity. Rilonacept inhibits both interleukin-1 alpha (IL-1α) and IL-1β; these cytokines are thought to play a major role in RP. This phase II study evaluated...