Acute mountain sickness, inflammation, and permeability: new insights from a blood biomarker study

The pathophysiology of acute mountain sickness (AMS) is unknown. One hypothesis is that hypoxia induces biochemical changes that disrupt the blood-brain barrier (BBB) and, subsequently, lead to the development of cerebral edema and the defining symptoms of AMS. This study explores the relationship between AMS and biomarkers thought to protect against or contribute to BBB disruption. Twenty healthy volunteers participated in a series of hypobaric hypoxia trials distinguished by pretreatment with placebo, acetazolamide (250 mg), or dexamethasone (4 mg), administered using a randomized, double-blind, placebo-controlled, crossover design. Each trial included peripheral blood sampling and AMS assessment before (-15 and 0 h) and during (0.5, 4, and 9 h) a 10-h hypoxic exposure (barometric pressure = 425 mmHg). Anti-inflammatory and/or anti-permeability [interleukin (IL)-1 receptor agonist (IL-1RA), heat shock protein (HSP)-70, and adrenomedullin], proinflammatory (IL-6, IL-8, IL-2, IL-1β, and substance P), angiogenic, or chemotactic biomarkers (macrophage inflammatory protein-1β, VEGF, TNF-α, monocyte chemotactic protein-1, and matrix metalloproteinase-9) were assessed. AMS-resistant subjects had higher IL-1RA (4 and 9 h and overall), HSP-70 (0 h and overall), and adrenomedullin (overall) compared with AMS-susceptible subjects. Acetazolamide raised IL-1RA and HSP-70 compared with placebo in AMS-susceptible subjects. Dexamethasone also increased HSP-70 and adrenomedullin in AMS-susceptible subjects. Macrophage inflammatory protein-1β was higher in AMS-susceptible than AMS-resistant subjects after 4 h of hypoxia; dexamethasone minimized this difference. Other biomarkers were unrelated to AMS. Resistance to AMS was accompanied by a marked anti-inflammatory and/or anti-permeability response that may have prevented downstream pathophysiological events leading to AMS. Conversely, AMS susceptibility does not appear to be related to an exaggerated inflammatory response.     

白细胞介素33通过促进上皮细胞黏附分子表达参与干燥综合征发病

摘要 目的：探讨白细胞介素（Interleukin-33,IL-33）可能通过调控上皮细胞黏附分子（Epithelial cell adhesion molecule, EpCAM）表达参与干燥综合征（Sj?gren''s syndrome, SS）发病的作用机制。方法：收集因SS诊断需要行唇腺活检术的患者血清和唇腺组织标本及相关临床资料,根据2016年ACR-EULAR SS分类诊断标准将患者分为SS组和非SS组,选取性别、年龄匹配的21例SS患者和21例非SS患者,利用多重检测流式试剂盒（人炎症因子组合1）检测血清中IL-33水平并用t检验比较SS患者组与非SS患者组、抗SSA抗体阳性与阴性组以及唇腺病理阳性与阴性组之间IL-33水平的差异。对唇腺组织石蜡切片进行IL-33免疫组织化学染色,用流式细胞术检测新鲜唇腺组织中上皮细胞EpCAM表达水平并与血清IL-33水平进行相关性分析。结果：SS患者组IL-33水平为（1736±590.1,n=21, pg/mL）,显著高于非SS患者组（306.8±120.3, n=21, pg/mL）（t=2.373,P=0.027）;唇腺病理阳性组即灶性血清IL-33水平（489.8±170, n=27, pg/mL）高于病理阴性组（1978±793.1, n=15, pg/mL）,2组之间有统计学差异（t=2.368,P=0.023）;而抗SSA抗体阳性组与阴性组之间无明显差异（P＞0.05）。免疫组化染色结果提示SS患者唇腺组织上皮细胞IL-33表达相较于非SS患者上升,且血清IL-33水平与唇腺上皮细胞EpCAM的表达呈中等强度正相关（r=0.4915,P=0.0009,95%CI 0.2205-0.692）。结论：IL-33是与SS密切相关的炎症因子,IL-33可能通过促进唾液腺上皮细胞EpCAM的表达参与SS发病。     

机械牵拉诱导人RPE细胞IL-8分泌及其对PI3K/AKT 通路的影响

目的:视网膜脱离发生机制尚不明确,本文旨在研究机械应力牵拉后视网膜色素上皮细胞上清中IL-8分泌量的变化以及人其对RPE细胞PI3K/AKT通路变化影响。方法:培养人RPE细胞,应用Flex-cell细胞应力加载系统牵拉人RPE细胞不同时间(0h、1 h、3 h、6 h、9 h)建立不同牵拉时间的模型。分别标记为对照组、牵拉1 h组、牵拉3 h组、牵拉6 h组、牵拉9 h组。随后用ELISA方法检测人RPE细胞不同实验组上清中IL-8分泌量的变化。细胞免疫荧光和Western blot方法观察PI3K、PPI3K、T-AKT、P-AKT的表达。结果:随着牵拉时间的延长,ELISA方法检测人RPE细胞不同实验组上清中IL-8分泌量逐渐增加[924.79±5.92 pg/m L、947.73±5.34 pg/m L、974.53±5.74 pg/m L、979.57±1.12 pg/m L、1019.22±4.25 pg/m L],差异有统计学意义(F=166,p0.01),各牵拉组与对照组分别对比,差异有统计学意义(P0.05)。细胞中P-AKT蛋白表达增加[0.61±0.02、0.97±0.05、0.99±0.04、1.21±0.11、1.20±0.07],差异有统计学意义(F=41.24,p0.01),各牵拉组与对照组分别对比,差异有统计学意义(P0.05),AKT表达未见明显变化。结论:机械应力牵拉人RPE细胞时,细胞上清中IL-8分泌量逐渐增加同时RPE细胞内PI3K/AKT通路明显激活,并与牵拉时间有关,为探究EMT原因和对防治PVR提供了理论基础。     

In vivo microdialysis sampling of cytokines produced in mice given bacterial lipopolysaccharide

Cytokines are proteins that mediate communication between cells of the immune system as well as certain other non-immune host cells. These proteins are produced by many cell types and they mediate immune and inflammatory responses. However, the direct site analysis of these critical proteins is hampered by the lack of site-specific tools available for such direct measurements. In this study, both in vitro and in vivo microdialysis sampling of different cytokines (tumor necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma], interleukin-6 [IL-6], IL-12p70, and macrophage chemoattractant protein-1 [MCP-1]) was performed. A mouse model of bacterial lipopolysaccharide (LPS) administration and response pattern was used for in vivo studies. Three cytokines, TNF-alpha, IL-6, and MCP-1 were quantified in the serum from mice given LPS. In vivo studies demonstrated the ability to monitor increasing levels of these cytokines (TNF-alpha, IL-6, and MCP-1) via microdialysis probes placed in the peritoneal cavity of mice given LPS. All three cytokines were quantified simultaneously in 15 muL of dialysate using a multiplexed bead-based immunoassay for flow cytometry. The detected dialysate cytokine concentrations varied between 200 pg/mL and 1500 pg/mL for TNF-alpha, between 600 pg/mL and 3000 pg/mL for MCP-1, and between 2700 pg/mL and more than 5000 pg/mL for IL-6. The detected serum cytokine concentrations ranged from 5700 pg/mL to 35,000 pg/mL for TNF-alpha, from 40,000 pg/mL to 65,000 pg/mL for MCP-1, and greater than than 100,000 pg/mL for IL-6. This work demonstrates that microdialysis sampling can be used in vivo to collect temporal profiles of cytokine production.     

羧甲司坦通过巯基上调HDAC2 抑制气道炎症

目的:探究羧甲司坦(carbocysteine,S-CMC)在气道炎症中对组蛋白去乙酰化酶2(histone deacetylase2,HDAC2)表达的调控作用和机制。方法:建立脂多糖(lipopolysaccharide,LPS)诱导大鼠肺泡巨噬细胞(NR8383)炎症模型、短期烟熏Sprague Dawely(SD)大鼠气道炎症模型,采用酶联免疫吸附测定法(enzyme-linked immunosorbent assay,ELISA)检测炎症因子白细胞介素6(interleukin-6,IL-6)和白细胞介素8(interleukin-8,IL-8)的水平,蛋白免疫印迹(Western blotting)及免疫组化染色检测HDAC2的表达。结果:与对照组相比,模型组NR8383细胞中HDAC2的表达明显降低至对照组的0.47±0.11倍,细胞上清IL-6、IL-8水平明显升高,分别为157.6±15.0 pg/m L、378.0±17.9 pg/m L;模型组SD大鼠肺组织中HDAC2的表达明显降低到对照组的0.42±0.12倍,气道灌洗液(bronchoalveolar lavage fluid,BALF)中IL-6、IL-8分别为162.2±51.4 pg/m L、331.4±62.7 pg/m L,炎症因子水平明显升高。而与模型组比较,经S-CMC处理后细胞中HDAC2表达明显上调至对照组的1.23±0.05倍,细胞上清中IL-6为92.3±4.3 pg/m L,IL-8为300.7±17.7 pg/m L,炎症因子水平降低;肺组织中HDAC2为对照组的0.78±0.10倍,表达水平明显升高,BALF中IL-6、IL-8水平分别为100.6±32.7 pg/m L,185.0±50.4 pg/m L(P0.05)炎症因子明显降低。组蛋白去乙酰化酶抑制剂曲古抑霉素A(trichostatin,TSA)能够抑制NR8383细胞中HDAC2的表达至对照组的0.19±0.06倍,增加IL-6(197.0±42.6 pg/m L)、IL-8(567.0±97.4 pg/m L)水平,该作用可以被S-CMC所逆转(P0.05)。另外,加入巯基供体二硫苏糖醇(dithiothreitol,DTT)可增强S-CMC上调HDAC2表达,降低IL-6、IL-8的作用,而巯基耗竭剂丁硫氨酸亚砜亚胺(buthionine-sulfoximine,BSO)可减弱S-CMC的作用(P0.05)。进一步表明S-CMC调控HDAC2的过程与巯基相关。结论:S-CMC可通过巯基上调HDAC2的表达抑制气道炎症。     

Correlation between levels of selected cytokines in cervico-vaginal fluid of women with abnormal vaginal bacterial flora

The aim of this study was to evaluate the rise of the levels of proinflammatory cytokines - IL-1alpha, IL-1beta, IL-6 and IL-8 in vagina of women with bacterial vaginosis (BV) and if there is any relationship between this levels. One hundred and twenty females between 22nd and 36th week of pregnancy were enrolled in the study. According to the bacterial flora of cervico-vaginal fluid evaluated by Gram stain, all women were divided into three groups. Group I (53 females; 44.2%)--normal bacterial flora, group II (35 females; 29.2%)--intermediate flora, and group with BV (32 females; 26.6%). The level of IL-1b in women with BV was over twelve times higher than in women from I group (131.35 and 10.6 pg/mL respectively). The next was the level of IL-1alpha--about seven times higher (128.45 vs 19.1 pg/mL) and the levels of IL-6 and IL-8, which were 1.7 times higher (16.2 vs 9.7 pg/mL and 656.7 vs 375.3 pg/mL respectively). Except for IL-6 these differences of levels were statistically significant (p<0.05). The levels of IL-1beta in group of women with BV correlated strongly with levels of IL-1alpha (r=0.72; p<0.0001) and weakly with levels of IL-6 (r=0.31; p=0.017). The correlation coefficient between levels of IL-6 and IL-8 rose gradually in II and BV group and reached levels r=0.575; p=0.0014 and r=0.67; p=0.0009 respectively. Our findings show that in vagina of women with BV the levels of proinflammatory cytokines rise, and that the rise of levels is in certain cases correlated.     

The human IL-17F/IL-17A heterodimeric cytokine signals through the IL-17RA/IL-17RC receptor complex

IL-17A and IL-17F, produced by the Th17 CD4(+) T cell lineage, have been linked to a variety of inflammatory and autoimmune conditions. We recently reported that activated human CD4(+) T cells produce not only IL-17A and IL-17F homodimers but also an IL-17F/IL-17A heterodimeric cytokine. All three cytokines can induce chemokine secretion from bronchial epithelial cells, albeit with different potencies. In this study, we used small interfering RNA and Abs to IL-17RA and IL-17RC to demonstrate that heterodimeric IL-17F/IL-17A cytokine activity is dependent on the IL-17RA/IL-17RC receptor complex. Interestingly, surface plasmon resonance studies indicate that the three cytokines bind to IL-17RC with comparable affinities, whereas they bind to IL-17RA with different affinities. Thus, we evaluated the effect of the soluble receptors on cytokine activity and we find that soluble receptors exhibit preferential cytokine blockade. IL-17A activity is inhibited by IL-17RA, IL-17F is inhibited by IL-17RC, and a combination of soluble IL-17RA/IL-17RC receptors is required for inhibition of the IL-17F/IL-17A activity. Altogether, these results indicate that human IL-17F/IL-17A cytokine can bind and signal through the same receptor complex as human IL-17F and IL-17A. However, the distinct affinities of the receptor components for IL-17A, IL-17F, and IL-17F/IL-17A heterodimer can be exploited to differentially affect the activity of these cytokines.     

Effect of Lifestyle Modification on Adipokine Levels in Obese Subjects with Insulin Resistance

Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty‐four insulin‐resistant obese subjects with varying degrees of glucose tolerance completed a 6‐month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)] and highly sensitive C‐reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 ± 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 ± 3 vs. 23.6 ± 3 ng/mL, p = 0.01) and IL‐6 (2.75 ± 1.51 vs. 2.3 ± 0.91 pg/mL, p = 0.012). TNF‐α levels tended to decrease (2.3 ± 0.2 vs. 1.9 ± 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C‐reactive protein (r = 0.466, p < 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL‐6 and a tendency toward a decrease in circulating TNF‐α, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.     

Serum levels of Th17 associated cytokines in chronic hepatitis C virus infection

The Th17-mediated immune response was investigated in patients chronically infected with hepatitis C virus (HCV) by determining the serum levels of the cytokines involved in the induction of the Th17 response (TGF-β and IL-6), the cytokines produced by Th17 cells (IL-17A, IL-17F and IL-22) and the cytokines whose production is stimulated by Th17 lymphocytes (IL-8 and GM-CSF). We investigated the relationships among the levels of these cytokines by assessing clinical findings, liver histology and viremia. Sixty untreated patients and 28 healthy individuals were included in the study. Cytokine levels were determined using ELISA. Differences between HCV and control groups were identified in the median levels of IL-17F (controls=172.4pg/mL; HCV=96.8pg/mL, p<0.001) and IL-8 (controls=30.1pg/mL; HCV=18.1pg/mL, p<0.05). IL-6 levels were higher in patients presenting moderate liver necroinflammation than in patients with mild or no liver necroinflammation (p<0.05). IL-17F levels were increased in patients that had increased ALT levels. Additionally, a strong positive correlation was observed between IL-17F and IL-22 levels in the two groups investigated, and the IL-17F/IL-22 ratio was lower in the patients infected with HCV (p<0.0001). Patients with low HCV viral loads had higher median levels of IL-8 (32.5pg/mL) than did patients with high HCV loads (16.7pg/mL, p<0.05). These results suggest that in chronic hepatitis C infection, IL-17F and IL-8 could be associated with the control of liver injury and infection, respectively.     

Can serum amyloid A or macrophage colony stimulating factor serve as marker of amyloid formation process?

Amyloid formation depends on amyloid precursor production and is influenced by the activity of the underlying disorder and mediated by some proinflammatory cytokines. In this pilot study we tried to find some specific markers that could establish the activity of the disease. We investigated 45 samples of sera and 38 samples of urine from patients (pts) with secondary amyloidosis (AA), primary amyloidosis (AL), systemic autoimmune diseases with renal impairment (Vasc) and healthy controls (Co). Pts with AA had increased plasma levels of TNF alpha (9.97 +/- 4.22 vs. 2.63 +/- 1.34 pg/mL, p < 0.001) and SAA (43.14 +/- 16.0 vs. 3.42 +/- 0.7 ng/mL, p < 0.05) in comparison with Co. Plasma levels of M-CSF in the AA group were significantly increased in comparison with Co (1077.34 +/- 238.6 vs. 137.71 +/- 19.6, pg/mL, p < 0.001) and also in comparison with Vasc (482.24 +/- 86.7 pg/mL, p < 0.05). Urinary excretions of TNF alpha (8.92 +/- 8.1 vs. 0.17 +/- 0.11 microgram/mol creatinine, p < 0.01), sIL-6R (1.39 +/- 1.14 vs. 0.07 +/- 0.05 g/mol creatinine, p < 0.01) and M-CSF (650.2 +/- 153.7 vs. 33.3 +/- 8.6 micrograms/mol creatinine, p < 0.01) in AA were significantly increased in comparison with Co. Pts with AL had increased plasma levels of M-CSF (819.83 +/- 264.2 vs. 137.71 +/- 19.6 pg/mL, p < 0.05) and urinary excretion of M-CSF (865.0 +/- 188.4 vs. 33.3 +/- 8.6 micrograms/mol creatinine, p < 0.01) in comparison with Co. SAA has a low specificity for amyloidosis but is a sensitive acute phase reactant. TNF alpha, a proinflammatory cytokine, may reflect the activity of the underlying diseases in secondary amyloidosis. M-CSF was increased both in plasma and urine in amyloidosis groups and seems to be the most promising (possibly specific) marker of amyloidosis.     

Enhancing effect of IL-1, IL-17, and TNF-alpha on macrophage inflammatory protein-3alpha production in rheumatoid arthritis: regulation by soluble receptors and Th2 cytokines.

Macrophage inflammatory protein (MIP)-3alpha is a chemokine involved in the migration of T cells and immature dendritic cells. To study the contribution of proinflammatory cytokines and chemokines to the recruitment of these cells in rheumatoid arthritis (RA) synovium, we looked at the effects of the monocyte-derived cytokines IL-1beta and TNF-alpha and the T cell-derived cytokine IL-17 on MIP-3alpha production by RA synoviocytes. Addition of IL-1beta, IL-17, and TNF-alpha induced MIP-3alpha production in a dose-dependent manner. At optimal concentrations, IL-1beta (100 pg/ml) was much more potent than IL-17 (100 ng/ml) and TNF-alpha (100 ng/ml). When combined at lower concentrations, a synergistic effect was observed. Conversely, the anti-inflammatory cytokines IL-4 and IL-13 inhibited MIP-3alpha production by activated synoviocytes, but IL-10 had no effect. Synovium explants produced higher levels of MIP-3alpha in RA than osteoarthritis synovium. MIP-3alpha-producing cells were located in the lining layer and perivascular infiltrates in close association with CD1a immature dendritic cells. Addition of exogenous IL-17 or IL-1beta to synovium explants increased MIP-3alpha production. Conversely, specific soluble receptors for IL-1beta, IL-17, and TNF-alpha inhibited MIP-3alpha production to various degrees, but 95% inhibition was obtained only when the three receptors were combined. Similar optimal inhibition was also obtained with IL-4, but IL-13 and IL-10 were less active. These findings indicate that interactions between monocyte and Th1 cell-derived cytokines contribute to the recruitment of T cells and dendritic cells by enhancing the production of MIP-3alpha by synoviocytes. The inhibitory effect observed with cytokine-specific inhibitors and Th2 cytokines may have therapeutic applications.     

间充质干细胞外泌体对海马星形胶质细胞活化的抑制作用研究

目的 探讨间充质干细胞外泌体(MSC-Exo)对海马星形胶质细胞活化的抑制作用.方法 实验通过超速离心法提取脐带MSC-Exo,并使用PKH-26染料标记;MSC-Exo预处理原代海马星形胶质细胞后使用脂多糖(LPS)诱导细胞活化,并分为对照组、LPS组和LPS+MSC-Exo组,进而行免疫细胞化学检测胶质纤维酸性蛋白...     

Obese reproductive-age women exhibit a proatherogenic inflammatory response during hyperglycemia

Objective: The objective was to determine if physiological hyperglycemia induces a proatherogenic inflammatory response in mononuclear cells (MNCs) in obese reproductive‐age women. Research Methods and Procedures: Seven obese and 6 age‐matched lean women (20 to 39 years of age) underwent a 2‐hour 75‐g oral glucose tolerance test. The release of interleukin‐6 (IL‐6) and interleukin‐1β (IL‐1β) from MNCs cultured in the presence of lipopolysaccharide (LPS) was measured after isolation from blood samples drawn fasting and 2 hours after glucose ingestion. Reactive oxygen species (ROS) generation and intra‐nuclear nuclear factor κB (NFκB) from MNCs were quantified from the same blood samples. Insulin resistance was estimated by homeostasis model assessment of insulin resistance (HOMA‐IR). Total body fat and truncal fat were determined by DXA. Results: Obese women had a higher (p < 0.03) total body fat (42.2 ± 1.1 vs. 27.7 ± 2.0%), truncal fat (42.1 ± 1.2 vs. 22.3 ± 2.4%), and HOMA‐IR (3.3 ± 0.5 vs. 1.8 ± 0.2). LPS‐stimulated IL‐6 release from MNCs was suppressed during hyperglycemia in lean subjects (1884 ± 495 vs. 638 ± 435 pg/mL, p < 0.05) but not in obese women (1184 ± 387 vs. 1403 ± 498 pg/mL). There was a difference (p < 0.05) between groups in the hyperglycemia‐induced MNC‐mediated release of IL‐6 (?1196 ± 475 vs. 219 ± 175 pg/mL) and IL‐1β (?79 ± 43 vs. 17 ± 12 pg/mL). In addition, the obese group exhibited increased (p < 0.05) MNC‐derived ROS generation (39.3 ± 9.9 vs. ?1.0 ± 12.8%) and intra‐nuclear NFκB (9.4 ± 7.3 vs. ?23.5 ± 13.5%). Truncal fat was positively correlated with the MNC‐derived IL‐6 response (ρ = 0.58, p < 0.05) and intra‐nuclear NFκB (ρ = 0.64, p < 0.05). Discussion: These data suggest that obese reproductive‐age women are unable to suppress proatherogenic inflammation during physiological hyperglycemia. Increased adiposity may be a significant contributor to this pro‐inflammatory susceptibility.     

Influence of metabolic syndrome on biomarkers of oxidative stress and inflammation in obese adults

Objective: Both obesity and the metabolic syndrome (MetS) have been independently linked with increased oxidative and inflammatory stress. This study tested the hypothesis that obesity with MetS is associated with greater oxidative and inflammatory burden compared with obesity alone. Research Methods and Procedures: Forty‐eight normal‐weight and 40 obese (20 without MetS; 20 with MetS) adults were studied. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. Plasma concentrations of oxidized low‐density lipoprotein, C‐reactive protein, tumor necrosis factor‐α, interleukin (IL)‐6, and IL‐18 were determined by enzyme immunoassay. Results: Plasma biomarkers of oxidative stress and inflammation were lowest in normal‐weight controls. Of note, obese MetS adults demonstrated significantly higher plasma concentrations of oxidized low‐density lipoprotein (62.3 ± 3.2 vs. 54.0 ± 4.0 U/L; p < 0.05), C‐reactive protein (3.0 ± 0.6 vs. 1.5 ± 0.3 mg/L; p < 0.01), tumor necrosis factor‐α (2.1 ± 0.1 vs. 1.6 ± 0.1 pg/mL; p < 0.05), IL‐6 (2.8 ± 0.4 vs. 1.4 ± 0.2 pg/mL; p < 0.01), and IL‐18 (253 ± 16 vs. 199 ± 16 pg/mL; p < 0.01), compared with obese adults without MetS. Discussion: These results suggest that MetS heightens oxidative stress and inflammatory burden in obese adults. Increased oxidative and inflammatory stress may contribute to the greater risk of coronary heart disease and cerebrovascular disease in obese adults with MetS.     

Effect of induced mild hypothermia on two pro-inflammatory cytokines and oxidative parameters during experimental acute sepsis

Abstract

This study aimed to determine the effect of induced mild hypothermia (34°C) on the production of two cytokines (interleukin (IL-6) and tumor necrosis factor (TNF)alpha) and reactive nitrogen and oxygen species in plasma and the heart of acutely septic rats. After anesthesia and in conditions of normothermia (38°C) or mild hypothermia (34°C), acute sepsis was induced by cecal ligation and perforation. For each temperature three groups were formed: (1) baseline (blood sample collected at T0 hour), (2) sham (blood sample at T4 hours) and (3) septic (blood sample at T4 hours). At either temperature sepsis induced a significant increase in plasma IL-6, TNF-alpha and HO^? concentration, compared with the sham groups (P ≤ 0.016). Compared with the normothermic septic group, septic rats exposed to mild hypothermia showed a mild decrease in TNF-alpha concentration (104 ± 50 pg/ml vs. 215 ± 114 pg/ml; P > 0.05) and a significant decrease in IL-6 (1131 ± 402 pg/ml vs. 2494 ± 691 pg/ml, P = 0.038). At either temperature sepsis induced no enhancement within the heart of lipoperoxidation (malondialdehyde content) or antioxidant activities (superoxide dismutase and catalase). In conclusion, during acute sepsis, induced mild hypothermia appears to reduce some pro-inflammatory and oxidative responses. This may, in part, explain the beneficial effect of hypothermia on survival duration of septic rats.     

Evidence that 19-hydroxyandrostenedione is secreted by the adrenal cortex and is under the control of ACTH and the renin-angiotensin system in man

Plasma 19-hydroxyandrostenedione (19-OH-A-dione) concentrations in man were evaluated using a specific and sensitive radioimmunoassay. Plasma 19-OH-A-dione concentrations (mean ± SE) in normal subjects are 151 ± 14 pg/ml (n=13) in males and 141 ± 9 pg/ml (n=14) in females. Plasma 19-OH-A-dione (mean ± SE) rises significantly during ACTH stimulation (116 ± 25 pg/ml vs 288 ± 38 pg/ml; P<0.01; n=5), declines significantly during dexamethasone suppression (180 ± 30 pg/ml vs 36 ± 14 pg/ml; P<0.01; n=4) and rises significantly during angiotensin II infusion (89 ± 10 pg/ml vs 159 ± 27 pg/ml; P<0.05; n=5). Plasma 19-OH-A-dione in the adrenal vein is much higher than that in the inferior vena cava (2076–3076 pg/ml vs 115–184 pg/ml; n=2). These results demonstrate that 19-OH-A-dione is directly secreted by the adrenal cortex and is under the control of ACTH and the renin-angiotensin system.     

HIV-1 inhibits phagocytosis and inflammatory cytokine responses of human monocyte-derived macrophages to P. falciparum infected erythrocytes

HIV-1 infection increases the risk and severity of malaria by poorly defined mechanisms. We investigated the effect of HIV-1_Ba-L infection of monocyte-derived macrophages (MDM) on phagocytosis of opsonised P. falciparum infected erythrocytes (IE) and subsequent proinflammatory cytokine secretion. Compared to mock-infected MDM, HIV-1 infection significantly inhibited phagocytosis of IE (median (IQR) (10 (0–28) versus (34 (27–108); IE internalised/100 MDM; p = 0.001) and decreased secretion of IL-6 (1,116 (352–3,387) versus 1,552 (889–6,331); pg/mL; p = 0.0078) and IL-1β (16 (7–21) versus 33 (27–65); pg/mL; p = 0.0078). Thus inadequate phagocytosis and cytokine production may contribute to impaired control of malaria in HIV-1 infected individuals.     

类风湿关节炎患者血清维生素D水平与疾病活动度相关

目的:探讨类风湿关节炎(Rheumatoid arthritis,RA)患者血清维生素D(25(OH)D)水平与疾病活动度的关系。方法:总共纳入180例RA患者,同时纳入60例年龄、性别相匹配的健康对照。检测所有参与者的血清25(OH)D水平及所有RA患者C反应蛋白和血沉。同时获取RA患者晨僵时间、疼痛视觉模拟表评分、乏力视觉模拟表评分、压痛关节数、肿胀关节数、健康评估量表得分、情绪变化量表得分等。利用RA患者28个关节疾病活动评分(Disease activity score in 28 joints,DAS28)评估RA疾病活动度。结果:相对于健康对照组(43.89±16.28 ng/m L),RA患者的血清25(OH)D明显降低(28.52±8.95 ng/m L)(P=0.000)。RA患者的血清25(OH)D水平越低,压痛关节数、肿胀关节数越多(P=0.043,r=-0.132;P=0.017,r=-0.177),血沉、C反应蛋白越高(P=0.018,r=-0.177;P=0.007,r=-0.200),同时DAS28评分越高(P=0.007,r=-0.201);患者的晨僵时间、疼痛评分、乏力评分、健康评估量表得分及情绪量表得分与血清维生素D水平负相关(P=0.043,r=-0.151;P=0.019,r=-0.175;P=0.006,r=-0.205;P=0.048,r=-0.147;P=0.017,r=-0.178)。结论:RA患者血清维生素D普遍缺乏,并且与RA患者疾病活动度负相关。