IL-6 Levels In Peripheral Blood Research Articles

Dietary administration of the glycolytic inhibitor 2-deoxy-D-glucose reduces endotoxemia-induced inflammation and oxidative stress: Implications in PAMP-associated acute and chronic pathology.

Pathogen-associated molecular patterns (PAMPs) like bacterial cell wall components and viral nucleic acids are known ligands of innate inflammatory receptors that trigger multiple inflammatory pathways that may result in acute inflammation and oxidative stress-driven tissue and organ toxicity. When dysregulated, this inflammation may lead to acute toxicity and multiorgan failure. Inflammatory events are often driven by high energy demands and macromolecular biosynthesis. Therefore, we proposed that targeting the metabolism of lipopolysaccharide (LPS)-driven inflammatory events, using an energy restriction approach, can be an effective strategy to prevent the acute or chronic detrimental effects of accidental or seasonal bacterial and other pathogenic exposures. In the present study, we investigated the potential of energy restriction mimetic agent (ERMA) 2-deoxy-D-glucose (2-DG) in targeting the metabolism of inflammatory events during LPS-elicited acute inflammatory response. Mice fed with 2-DG as a dietary component in drinking water showed reduced LPS-driven inflammatory processes. Dietary 2-DG reduced LPS-induced lung endothelial damage and oxidative stress by strengthening the antioxidant defense system and limiting the activation and expression of inflammatory proteins, viz., P-Stat-3, NfκΒ, and MAP kinases. This was accompanied by decreased TNF, IL-1β, and IL-6 levels in peripheral blood and bronchoalveolar lavage fluid (BALF). 2-DG also reduced the infiltration of PMNCs (polymorphonuclear cells) in inflamed tissues. Altered glycolysis and improved mitochondrial activity in 2-DG-treated RAW 264.7 macrophage cells suggested possible impairment of macrophage metabolism and, therefore, activation in macrophages. Taken together, the present study suggests that inclusion of glycolytic inhibitor 2-DG as a part of the diet can be helpful in preventing the severity and poor prognosis associated with inflammatory events during bacterial and other pathogenic exposures.

Akkermansia muciniphila Ameliorates Lung Injury in Smoke-Induced COPD Mice by IL-17 and Autophagy

Objective. Smoking is a primary hazard factor for chronic obstructive pulmonary disease (COPD), which induced a decrease in intestinal Akkermansia muciniphila abundance and Th17 imbalance in COPD. This study analyzed the changes of gut microbiota metabolism and Akkermansia abundance in patients with smoking-related COPD and explored the potential function of Akkermansia muciniphila in smoke-induced COPD mice. Methods. Gut microbiota diversity and metabolic profile were analyzed by 16S rRNA sequence and metabolomics in COPD patients. The IL-1β, IL-17, TNF-α, and IL-6 levels were tested by ELISA. Lung tissue damage was observed by HE staining. The expression of cleave-caspase 3, trophoblast antigen 2 (TROP2), and LC3 in lung tissues were analyzed by IHC or IF. The p-mTOR, mTOR, p62, and LC3 expression in lung tissues were tested by western blot. Results. The levels of IL-17, IL-1β, TNF-α, and IL-6 in the peripheral blood of COPD patients increased significantly. The number and alpha diversity of gut microbiota were decreased in COPD patients. The abundance of Akkermansia muciniphila in gut of COPD patients was decreased, and the metabolic phenotype and retinol metabolism were changed. In the retinol metabolism, the retinol and retinal were significantly changed. Akkermansia muciniphila could improve the alveolar structure and inflammatory cell infiltration in lung tissue, reduce the IL-17, TNF-α, and IL-6 levels in peripheral blood, promote the p-mTOR expression, and inhibit the expression of autophagy-related proteins in smoke-induced COPD mice. Conclusion. The number and alpha diversity of gut microbiota were decreased in patients with smoking-related COPD, accompanied by decreased abundance of Akkermansia muciniphila, and altered retinol metabolism function. Gut Akkermansia muciniphila ameliorated lung injury in smoke-induced COPD mice by inflammation and autophagy.

Levels of IL-6 in peripheral blood and cerebrospinal fluid of Alzheimer's disease: a meta-analysis

BACKGROUND: Alzheimer's disease (AD) is a common degenerative disease of the central nervous system in the elderly. Several reports have described the serum levels of interleukin (IL-6) in AD. In order to elucidate the status of IL-6 in AD, the article conducted a meta-analysis of previously published results to assess the levels of IL-6 from different tissue sources in AD. METHODS: The levels of Th17 related cytokines (IL-6) in peripheral blood or cerebrospinal fluid (CSF) of AD were systematically reported in domestic and foreign databases. The article assessed pooled data using a random-effects model.The I-square index (I2) was used to assess inconsistency and publication bias was assessed by examining funnel plot asymmetry using the Begg and Egger test. Results: Among 1348 identified studies, the article selected 45 studies for analysis, 36 to investigate IL-6 levels in peripheral blood and 9 to investigate IL-6 levels in CSF of AD versus healthy controls (HCs). The analysis revealed that IL-6 content in peripheral blood of AD was significantly higher than that of HCs[SMD = 0.913, 95% CI (0.345, 1.481), P < 0.05], while the level of IL-6 in CSF showed no statistical significance [SMD = 0.132, 95% CI (-0.579, 0.843), P > 0.05] and could not be used as a marker in AD. CONCLUSIONS: In AD, the level of IL-6, a relevant marker, is increased, and spontaneous IL-6 production by peripheral blood mononuclear cells may be a marker of future AD risk in the elderly, and these data strengthen evidence of the pathophysiological role of inflammation in the development of clinical AD, but suggest that the mechanism of IL-6 action still needs more research and can be used as a potential target to address the problem of AD in the future.

Anzi Heji Downregulates DNMT1 to Improve Anticardiolipin Antibody (ACA)-Positive Abortion by Regulating JAK/STAT Pathway

Anzi Heji (AZHJ) is a traditional Chinese medicine compound prepared for long-term treatment of Anticardiolipin Antibody (ACA)-positive abortion, with small side effects and definite curative effect. Abortion was reported to be related to DNMT1, a methylation transferase regulated by JAK2 pathway, so this study aimed to explore whether AZHJ treated ACA-positive abortion by regulating the DNMT1. Cell proliferation estimation employed Cell counting kit-8 (CCK-8) and flow cytometry. Human β2-glycoprotein I (GPI) was used as an inducer to establish ACA-positive mice model. Western blot was applied to examine the expressions of DNMT1, FOXP3, IL-6, and JAK/STAT3 pathway-related proteins. ACA titers and IL-6 levels in peripheral blood were tested by enzyme-linked immunosorbent assay (ELISA). Placental tissue damage was assessed by hematoxylin and eosin (H&amp;E) staining. Based on the findings from experiments, AZHJ could significantly inhibit apoptosis and regulate the proliferation activity of HTR-8/SVneo cells. AZHJ treatment reduced the expression levels of DNMT1, FOXP3, IL-6, and JAK/STAT3 signaling pathways-related proteins in HTR-8/SVneo cells and maternal–fetal interface (uterine decidua and placenta), and the titer of serum ACA was also significantly decreased. In addition, AZHJ effectively alleviated placental tissue damage caused by ACA-positive abortion compared with model group. To sum up, AZHJ may play a therapeutic role by inhibiting DNMT1 activation through Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, and then promoting FOXP3 expression in maternal–fetal interface of pregnant mice, thereby improving immune tolerance at the maternal–fetal interface, preventing and treating ACA-positive abortion.

Successful Treatment with Intrathecal Tocilizumab(IL-6 antibody) for 2 Cases of Graft-Versus Host Disease of the Central Nervous System after a Second Allogeneic HSCT from Haploidentical Donor

Graft-versus-host disease (GVHD) of central nervous system (CNS) is a rare complication after allogeneic hematopoietic cell transplantation (allo-HSCT), which is easily misdiagnosed and has limited treatment and poor efficacy. In this study, we reported two children(1 case of severe aplastic anemia and 1 case of acute myeloid leukemia) who were subjected to the secondary haploid hematopoietic stem cell transplantation of another door after the first implantation failure. Two patients developed epileptic seizures during hematopoietic recovery. Peripheral blood and cerebrospinal fluid cytokines were detected and diagnosed as acute GVHD in the central nervous system. The cytokine elevation is mainly IL-6(IL-6 level in peripheral blood was 2276.25 pg/ml, and in cerebrospinal fluid was 2353.89pg/ml of case 1). We administered multiply consecutive plasmapheresis, intravenous infusion of tocilizumab combined with intrathecal injection of tocilizumab and dexamethasone. The epileptic symptoms of 2 cases are effectively controlled after the first dose. The IL-6 levels in peripheral blood and cerebrospinal fluid of both patients decreased significantly after 4(IL-6 level in peripheral blood was 6.74 pg/ml, and in cerebrospinal fluid was 195.72pg/ml of case 1) and 5 doses, respectively. Central nervous system aGVHD is prone to hematopoietic recovery after secondary transplantation; intrathecal injection of tocilizumab is safe and effective in the treatment of central nervous system aGVHD with elevated IL-6 mainly, which is worth further exploring. DisclosuresNo relevant conflicts of interest to declare.

Systemic inflammation disrupts oligodendrocyte gap junctions and induces ER stress in a model of CNS manifestations of X-linked Charcot-Marie-Tooth disease.

X-linked Charcot-Marie-Tooth disease (CMT1X) is a common form of inherited neuropathy resulting from different mutations affecting the gap junction (GJ) protein connexin32 (Cx32). A subset of CMT1X patients may additionally present with acute fulminant CNS dysfunction, typically triggered by conditions of systemic inflammation and metabolic stress. To clarify the underlying mechanisms of CNS phenotypes in CMT1X we studied a mouse model of systemic inflammation induced by lipopolysaccharide (LPS) injection to compare wild type (WT), connexin32 (Cx32) knockout (KO), and KO T55I mice expressing the T55I Cx32 mutation associated with CNS phenotypes. Following a single intraperitoneal LPS or saline (controls) injection at the age of 40–60 days systemic inflammatory response was documented by elevated TNF-α and IL-6 levels in peripheral blood and mice were evaluated 1 week after injection. Behavioral analysis showed graded impairment of motor performance in LPS treated mice, worse in KO T55I than in Cx32 KO and in Cx32 KO worse than WT. Iba1 immunostaining revealed widespread inflammation in LPS treated mice with diffusely activated microglia throughout the CNS. Immunostaining for the remaining major oligodendrocyte connexin Cx47 and for its astrocytic partner Cx43 revealed widely reduced expression of Cx43 and loss of Cx47 GJs in oligodendrocytes. Real-time PCR and immunoblot analysis indicated primarily a down regulation of Cx43 expression with secondary loss of Cx47 membrane localization. Inflammatory changes and connexin alterations were most severe in the KO T55I group. To examine why the presence of the T55I mutant exacerbates pathology even more than in Cx32 KO mice, we analyzed the expression of ER-stress markers BiP, Fas and CHOP by immunostaining, immunoblot and Real-time PCR. All markers were increased in LPS treated KO T55I mice more than in other genotypes. In conclusion, LPS induced neuroinflammation causes disruption of the main astrocyte-oligodendrocyte GJs, which may contribute to the increased sensitivity of Cx32 KO mice to LPS and of patients with CMT1X to various stressors. Moreover the presence of an intracellularly retained, misfolded CMT1X mutant such as T55I induces ER stress under inflammatory conditions, further exacerbating oligodendrocyte dysfunction and pathological changes in the CNS.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-016-0369-5) contains supplementary material, which is available to authorized users.

The changes and its significance of Th17 and Treg cells and related cytokines in patients with tuberculosis pleurisy.

BackgroundTuberculous pleurisy is a kind of tuberculosis, it is well known that Th1 lymphocytes play a key role in the treatment of tuberculosis infection. However, latest studies show that Th17 lymphocyte may also play an important role tuberculosis infection. There is close relationship between Treg and Thl7 cells, and changes in the number or the function of the two kinds of cells may lead to diseases. The current researches on Thl7 and Treg cells maily focus on autoimmune diseases, however, reports about their role in tuberculosis are limited. In this study, we investigate the function of th17 and Treg cells and the above cytokines in the pathogenesis of tuberculosis pleurisy; by determining the expression of Th17 and Treg cells in peripheral CD4 T cells and the related cytokines in patients with tuberculous compared with healthy people.ResultsTh17 cells in patients were higher than that in the Healthy control group, expression of Treg cells in patients were lower than that in the healthy group; IL-17, IL-23 levels in peripheral blood and hydrothorax from the patients were higher than that in the healthy group; IL-17, IL-23 and IL-6 levels in hydrothorax were higher than that in peripheral blood. There was no difference in IL-6 level in peripheral blood between the patients and healthy control; TGF- β level in peripheral blood from the healthy group was higher than that in peripheral blood and hydrothorax from the patients. And there were no differences in TGF- β level between peripheral blood and hydrothorax. Th17 cells were negatively correlated with Treg cells ,but were positive correlation with IL-17, IL-23, IL-6 levels in peripheral blood; TGF- β level was positive correlation with Treg cells in the peripheral blood, but no correlation with Th17 cells.ConclusionTh17 and Treg cells may be involved in the immune pathological mechanism of tuberculous pleurisy and changes of related cytokines may be involved in the differentiation of Th17 and Treg cells and inflammatory response. Thus, Th17 and Treg cells and related cytokines may be important immunopathogenesis for tuberculous pleurisy.

Changes of Th17 cells, Treg cells and Th17/Treg cell-associated cytokines in patients with tubercu-lous pleurisy and significance of the changes

Objective To investigate the significance of Th 17 cells, Treg cells and Th17/Treg cell-associated cytokines in the development of tuberculous pleurisy through detecting the expressions of Th 17 cells and Treg cells （CD4＋CD25＋Foxp3＋） in CD4＋T cells, analyzing concentrations of IL-17, IL-23, IL-6＆nbsp;and TGF-βin serum of patients with tuberculous pleurisy and healthy controls and measuring levels of IL -17, IL-23, IL-6 and TGF-βin hydrothorax of patients with tuberculous pleurisy .Methods Flow cytometry was used to detect expressions of Th 17 and Treg cells in peripheral blood of patients with tuberculous pleurisy and healthy controls.ELISA method was performed for quantitative detection of concentrations of IL -17, IL-23, IL-6 and TGF-βin serum and hydrothorax .Differences and correlations between the above measured data were analyzed by the statistical software SPSS 17.0.Results Compared with the healthy control group , the expressions of Th17 cells in peripheral blood of the patients were significantly increased （1.02%±0.20%vs.0.89%±0.13%, P=0.002〈0.05）, while the expressions of Treg cells were significantly decreased （4.64%±0.77%vs.5.10%±0.90%, P=0.000〈0.05）.Correspondingly, the ratio of Th17/Treg cells （0.25±0.07） in the patients were significantly higher than that in the healthy controls （0.17±0.05, P=0.000〈0.05）.Concentrations of IL-17, IL-23 and IL-6 in peripheral blood and in hydrothorax of the pa-tients were （17.49±3.94） ng/L, （90.42±23.06） ng/L, （4.54±1.02） ng/L and （26.13±5.98） ng/L, （122.26±31.71） ng/L, （5.31±0.74） ng/L respectively, which were remarkably higher than the levels of IL-17 （14.45±3.81） ng/L, IL-23 （77.55±20.26） ng/L and IL-6 （4.26±0.91） ng/L in control group. In tuberculous pleurisy group , concentrations of IL-17, IL-23 and IL-6 in hydrothorax were significantly higher than those in peripheral blood with P values of 0.000, 0.000 and 0.003.There was no difference be-tween IL-6 levels in peripheral blood from patients and IL-6 levels in peripheral blood from the healthy con-trols, P=0.274.In comparison with the control group , TGF-βlevels in peripheral blood and in hydrothorax of the patients were significantly decreased （3.95 ng/L±0.79 ng/L, 3.12 ng/L±0.77 ng/L vs.3.32 ng/L ±0.80 ng/L） .In tuberculous pleurisy patients , the expression of Th17 cells in peripheral blood was nega-tively correlated with Treg cells in peripheral blood （r=-0.684, P=0.000〈0.05）, but was positively relat-ed to the levels of IL-17, IL-23 and IL-6 （r=0.479, 0.441, 0.326, P=0.013, 0.015, 0.017）.TGF-βlevel had significantly positive correlations with Treg cells in the peripheral blood of the patients （r=0.297, P=0.024）, but no significant correlation with Th17 cells was found （r=0.091, P=0.659）.Conclusion Th17/Treg cell-associated cytokines might regulate the expressions of Th 17 and Treg cells and inflammatory reaction.Changes of Th17 cells, Treg cells and related cytokines might be important immunopathological mechanisms for tuberculous pleurisy . Key words: Th17 cell; Treg cell; Tuberculous pleurisy; Flow cytometry; Cytokine

Oral administration of ginsenoside Rh1 inhibits the development of atopic dermatitis-like skin lesions induced by oxazolone in hairless mice

In the present study, we examined the inhibitive effect of ginsenoside Rh1 on oxazolone-induced atopic dermatitis-like skin lesions in hairless mice. Oral administration of ginsenoside Rh1 improved clinical symptoms, and it was confirmed by histophathological analysis. In ginsenoside Rh1 (20 mg/kg) group, ear swellings and ear weights were significantly lower than the control group. Moreover, elevation of IL-6 and total IgE levels in serum were suppressed by ginsenoside Rh1 (20 mg/kg). In addition, ginsenoside Rh1 (20 mg/kg) significantly increased mRNA expression of IFNγ and Foxp3, and slightly decreased IL-4 expression in draining lymph nodes. The results suggest that ginsenoside Rh1 can alleviate inflammatory symptoms in atopic dermatitis (AD) by reduction of IgE and IL-6 levels in peripheral blood, increase of Foxp3 expression in draining lymph nodes and suppression of inflammation in skin regions. Indeed, ginsenoside Rh1 exhibited therapeutic possibility in immune disorders.

The Level of Interleukin-6 in Coronary sinus and peripheral blood in patiens with unstable angina after coronary intervention

Background：It has not been completely understood whether acute phase responses of unstable angina result from a disruption of coronary plaques or from an instability & hypersensitivity of the plaque itself. Plasma IL6 can be affected by several systemic factors, so it is difficult to conclude that IL-6 level in the peripheral blood always reflects the level of the coronary sinus blood. Methods：We measured the IL-6 level in coronary sinus blood and peripheral blood of 14 patients (11 men, 3 women, mean age 55±6 years, range 43 to 65 years with unstable angina before, and 4, 8, 16, 24, and 36 hours after undergoing percutaneous coronary intervention (PCI, respectively. Results：A statistically significant increase of all IL-6 levels in both coronary sinus blood and peripheral blood following PCI was noted. There was also a correlation between IL-6 levels in coronary sinus blood and peripheral blood following PCI (correlation coefficient r＝0.416, p＝0.01, although the difference of the concentration of IL-6 between coronary sinus blood and peripheral blood following PCI was increased as time passed. There was no statistically significant relationship between the number of coronary lesions treated with PCI and the amount of elevation of plasma IL-6 level. Conclusion：It is difficult to infer that the IL-6 level in peripheral blood exactly reflects the level found in the coronary sinus blood and the plaque rupture induced by PCI is the main cause of the elevated plasma IL-6.(Korean Circulation J 2001;31(8 :773-779

Parasite virulence factors during falciparum malaria: rosetting, cytoadherence, and modulation of cytoadherence by cytokines

To determine virulence factors of isolates of Plasmodium falciparum and the potential role of cytokines in cerebral malaria, 46 Malagasy patients presenting with cerebral (n = 10), severe (n = 10), and uncomplicated (n = 26) malaria were enrolled in a study. The capacity of 21 of 46 P. falciparum isolates to form rosettes in vitro and to adhere to human umbilical vein endothelial cells (HUVECs) that express intercellular adhesion molecule-1 receptors and to C32 amelanotic melanoma cells that express mainly CD36 receptors was investigated together with the effects of tumor necrosis factor alpha (TNF-alpha), granulocyte macrophage-colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and IL-6 alone and in two-by-two combinations on the cytoadherence of infected erythrocytes to HUVECs. Plasma levels of these cytokines were also measured in the patients at admission. The percentage of rosette formation was higher for the isolates from patients with cerebral (n = 6; 19.5%) and severe (n = 6; 30.5%) malaria than for those from patients with uncomplicated malaria (n = 9; 5%) (P < 0.002). The cytoadherence properties of the isolates did not differ among the three groups whatever the target cell used, but adherence to melanoma cells was systematically higher than that to HUVECs. Adhesion to HUVECs was increased more after TNF-alpha stimulation than after GM-CSF, IL-3, or IL-6 stimulation (P < 0.01). Only the combination of TNF-alpha and IL-3 enhanced cytoadherence more than TNF-alpha used alone (P < 0.02). No difference in the modulation of cytoadherence by cytokines was found in relation to the severity of the disease. TNF-alpha and IL-6 levels in peripheral blood were higher in the patients with cerebral and severe malaria than in the patients with uncomplicated malaria (P < 0.005). Most of the patients' sera contained little or no IL-3 or GM-CSF. Our results challenge the role of intercellular adhesion molecule-1 as the principal receptor mediating the cytoadherence of P. falciparum-infected erythrocytes and contrast with data obtained in the murine model.