慢性盆腔炎患者促炎因子与抗炎因子的关系

目的:探讨慢性盆腔炎患者血清促炎因子与抗炎因子的表达与相关性。方法:选择87例慢性盆腔炎患者作为病例组,选择同期健康体检妇女69例作为对照组,ELISA法检测血清TNF-α、IL-1β、IL-6和抗炎细胞因子IL-4、IL-10的表达。结果:病例组患者血清TNF-α、IL-1β和IL-6表达高于对照组(P<0.05),而血清IL-4和IL-10表达低于对照组(P<0.05);病例组患者血清促炎因子的表达与抗炎因子的表达呈负相关(P<0.05)。结论:慢性盆腔炎患者促炎因子过度激活,而抗炎因子被抑制,并且二者表达具有一定的相关性,共同促进慢性盆腔炎的发生发展。     

婴幼儿肺炎支原体感染促炎/抗炎细胞因子水平的动态变化及其诊断价值

目的:探讨婴幼儿肺炎支原体肺炎(MPP)促炎细胞因子和抗炎细胞因子水平的动态变化,探讨其临床意义及诊断价值。方法:收集疑似MP感染患儿73例,健康体检儿童60例,采用血清学方法检测MP-IgM,并分离培养鉴定MP;采用ELISA法测定MPP患儿急性期、恢复期及对照组促炎细胞因子(TNF-α、IL-8)和抗炎细胞因子(IL-10、IL-13)的水平。通过ROC曲线分析曲线下面积(AUC),比较各细胞因子对MPP的诊断效率,计算其敏感度和特异度。结果:经实验室检查,确诊MPP患儿46例,MPP患儿急性期促炎细胞因子(TNF-α、IL-8)水平明显高于恢复期及健康对照组,差异有统计学意义(P<0.05);急性期抗炎细胞因子IL-10水平明显低于恢复期和健康对照组,差异有统计学意义(P<0.05);急性期抗炎细胞因子IL-13水平明显高于恢复期和健康对照组,差异有统计学意义(P<0.05)。ROC曲线结果显示4种细胞因子AUC分别为0.768、0.862、0.564和0.717,IL-8在MPP中有较高的诊断价值(AUC接近0.9),其最佳分界值为102.57 pg/ml,诊断MPP的敏感度及特异度分别为78.2和89.1。结论:婴幼儿MPP发病过程中,促炎细胞因子(TNF-α、IL-8)始终处于高表达状态,抗炎因子IL-10低水平表达可能与MPP发病有关,提示机体免疫调节失控,同时以IL-13高水平表达的抗感染反应占优势。通过ROC曲线分析,IL-8可作为辅助诊断MPP的实用指标。     

A jerte valley cherry product provides beneficial effects on sleep quality. Influence on aging

Objective

In the present work, we evaluated the effect of the intake of a Jerte Valley cherry-based product (JVCP), compared to a placebo product, on sleep quality, urinary 6-sulfatoxymelatonin (aMT6-s) levels and the serum concentration of interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8).

Design

This was a blind, placebo-controlled, randomized, crossover study.

Setting

University of Extremadura (Spain).

Participants

Ten young (20–30 years old), ten middle-aged (35–55 years old), and ten elderly (65–85 years old) participants.

Intervention

A placebo (Kool-Aid®) or JVCP (patent no. ES 2342141 B1) were consumed twice a day, as lunch and dinner desserts.

Measurements

Actigraphic monitoring was used to record and display the temporal patterns of the individuals’ activity and rest. Urinary aMT6-s and serum cytokines (IL-1β, TNF-α and IL-8) were also determined.

Results

The consumption of the JVCP improved the nocturnal rest, measured by sleep efficiency, number of awakenings, total nocturnal activity, sleep latency, assumed sleep, actual sleep time and immobility. Moreover, it was detected an increase in both the levels of aMT6-s found in first-void morning urine and the concentrations of serum pro-somnogenic cytokines obtained from samples collected at the acrophase of the melatonin rhythm (1.00 am) in all experimental age groups after the JVCP consumption. Generally, better results were obtained with advancing age.

Conclusion

The ingestion of the JVCP may contribute to establish a high-quality sleep and be used as a potential nutraceutical tool to prevent sleep disorders with the advance of age.     

Lipopolysaccharide (LPS) induced activation of the immune system in control rats and rats chronically exposed to a low level of the organothiophosphate insecticide, acephate

Lipopolysaccharide (LPS), a key inflammatory component of gram-negative bacteria, induces a distinctive pattern of cytokine release that regulates inflammation. An alteration in the LPS response may play a fundamental role in the pathogenesis of a number of inflammatory diseases. Therefore, this study was conducted to determine whether chronic exposure to a low level of acephate (Ace), a commonly used organophosphate insecticide, impaired the LPS response in rats. This study showed that LPS injection in control rats caused (1) a time-dependent increase in blood lymphocyte enumeration and differentiation, and (2) a sequential increase the pro-inflammatory (interleukin-1beta (IL1beta), tumor necrosis factor-alpha (TNFalpha), interferon-gamma (INTgamma), and inducible nitric oxide synthase (iNOS)) and anti-inflammatory (interleukin-4 (IL-4), corticotropin-releasing factor (CRF), and blood corticosterone (Cort)) cytokines. The pro-inflammatory cytokines increased after 30 min, while the anti-inflammatory cytokines increased 3 h after LPS injection. An increase in proinflammatory cytokines increased lymphocyte enumeration and differentiation, while the increase in anti-inflammatory cytokines re-established homeostasis. In comparison to the control rats, the Ace-exposed rats exhibited (1) lower levels of IL1beta, TNFalpha and iNOS, (2) higher levels of CRF and Cort, and (3) lower levels of IL-4 in blood and/or brain samples. The abnormal cytokine production may be associated with abnormal phenotypic distribution of B and T cells. Blood IgMhi IgDhi, IgMlo IgDlo and CD8+ CD45RA- CCR7+ cells were elevated, while IgMlo IgDhi, IgMhi IgDlo, IgMin IgDlo, CD8+ CD45RA+ CCR7+ and CD8+ CD45RA- CCR7 cells were depressed in Ace-exposed rats. Thus, chronic low-level Ace exposure may impair the lineage commitment in lymphocytes, possibly by altering cytokine signaling in the brain.     

IL-6家族细胞因子在肺纤维化中的作用

肺纤维化是以成纤维细胞增殖、大量细胞外基质聚集,以及伴随炎症损伤、组织结构破坏为特征的一大类肺疾病的终末期改变;炎症反应在纤维化发病过程中尤其起到关键作用。白细胞介素-6( interleukin-6, IL-6)家族细胞因子作为促炎细胞因子或抗炎细胞因子参与肺部炎症反应,通过调控促纤维化因子分泌,激活信号传导通路,诱导成纤维细胞的增殖、分化,从而在肺纤维化进展中发挥重要作用。本文拟对IL-6家族细胞因子在肺纤维化中的作用与治疗研究进行综述,以供今后工作参考。     

Dietary fish oil increases tumor necrosis factor secretion but decreases interleukin-10 secretion by murine peritoneal macrophages

Dietary fish oil has immunomodulatory effects that are mediated in part by its effects on cytokines. Secretion of the inflammatory and the anti-inflammatory cytokines tumor necrosis factor (TNF) and interleukin (IL)-10 by murine resident peritoneal macrophages was monitored after ex vivo stimulation with lipopolysaccharide. Macrophages were obtained from mice fed a corn oil diet containing 200 g/kg corn oil or a fish oil diet containing 180 g/kg fish oil and 20 g/kg corn oil. Dietary fish oil increased secretion of the proinflammatory cytokine, TNF, but decreased secretion of the anti-inflammatory cytokine, IL-10. The cytokines appeared in the medium after 1.5 h and peaked at 6-12 h. Neutralizing antibodies against TNF and IL-10 had little effect on secretion of the other cytokine, indicating that the effects of fish oil on TNF and IL-10 secretion by these cells are independent of one another. Furthermore, although inhibiting prostaglandin production enhanced TNF secretion by macrophages from mice fed the corn oil diet, it did not affect IL-10 secretion by macrophages in this group. Blocking leukotriene B(4) production also did not affect IL-10 secretion in macrophages from mice fed a nonpurified diet. These results demonstrate that fish oil has an overall pro-inflammatory effect given its effects on secretion of both inflammatory and anti-inflammatory cytokines by resident peritoneal macrophages.     

Dietary β-glucan regulates the levels of inflammatory factors, inflammatory cytokines, and immunoglobulins in interleukin-10 knockout mice

β-Glucan is known to have anti-inflammatory properties, and several studies have demonstrated the beneficial effects of dietary β-glucan on inflammatory bowel disease (IBD). However, it is unknown how β-glucan mediates its protective effects on IBD. Therefore, we used a well-established mouse model for IBD, interleukin (IL)-10(-/-) mice, to explore the protective effects of β-glucan on IBD-like symptoms caused by IL-10 deficiency. The mice were divided into two groups: IL-10(-/-) and IL-10(-/-)?+?β-glucan treatment groups. IL-10(-/-) mice treated with dietary β-glucan exhibited less inflammation within the colon. The levels of immunoglobulins A and E were lower in the serum, spleen, mesenteric lymph nodes, and Peyer's patches in the IL-10(-/-) mice compared with the IL-10(-/-)?+?β-glucan mice. Also, the expression of pro-inflammatory cytokines was lower in the IL-10(-/-)?+?β-glucan mice compared with the IL-10(-/-) mice. Histological analysis also revealed that administration of dietary β-glucan in IL-10(-/-) mice reduced colonic tissue damage. Finally, the expression of the pro-inflammatory cytokine tissue necrosis factor-α was significantly lower with dietary β-glucan treatment in IL-10(-/-) mice. In conclusion, dietary β-glucan reduces the inflammation associated with IBD caused by IL-10 deficiency.     

Lower genital tract inflammatory milieu and the risk of subsequent preterm birth: an exploratory factor analysis

The inflammatory milieu of the cervix may play a role in preventing intrauterine infection and subsequent preterm birth. The objectives of this study were to use exploratory factor analysis to discover the underlying structure of cytokines in the lower genital tract immunological milieu, and evaluate the association between the cytokine factors and risk of preterm birth. Women (n=613) enrolled in a prospective pregnancy cohort study in Pittsburgh, Pennsylvania had cervical cytokine concentrations assayed at <16 weeks and were followed for data on pregnancy outcomes. Principal factor analysis identified two primary cytokine patterns at <16 weeks gestation: Factor 1 (pro-inflammatory/immunomodulatory factor), which loaded highly on interleukin (IL)-1β, IL-6, IL-8, monocyte chemotactic protein-1, and IL-10, and Factor 2 (anti-inflammatory factor), which loaded heavily on IL-4, IL-10, and IL-13. Women in the highest tertile of anti-inflammatory cytokine factor scores at <16 weeks had an increased risk of spontaneous preterm birth (confounder-adjusted odds ratio [95% confidence interval]: 2.4 [1.1, 5.7]). There was no association between pro-inflammatory cytokine factor scores and preterm birth risk. These data support the hypothesis that increased concentrations of anti-inflammatory cytokines may represent a cervical immune milieu that permits subsequent microbial invasion of the uterus during pregnancy, leading to subsequent spontaneous preterm birth.     

Supplementing alpha-tocopherol (vitamin E) and vitamin D3 in high fat diet decrease IL-6 production in murine epididymal adipose tissue and 3T3-L1 adipocytes following LPS stimulation

Background  

It is well known that high fat diets (HFDs) induce obesity and an increase in proinflammatory adipokines. Interleukin-6 (IL-6) is considered the major inflammatory mediator in obesity. Obesity is associated with a vitamin deficiency, especially of vitamins E and D3. We examined the effects of vitamin D3 and vitamin E supplementation on levels of IL-6 and IL-10 (as a marker of anti-inflammatory cytokines since, a balance between pro- and anti-inflammatory cytokines is maintained) protein expression in adipose tissue of mice provided with an HFD. Additionally, we measured the effects of vitamin E and vitamin D3 treatment on LPS-stimulated 3T3-L1 adipocytes IL-6 and IL-10 secretion.     

Modulating effect of glutamine on IL-1beta-induced cytokine production by human gut

BACKGROUND & AIMS: Balance between pro-and anti-inflammatory mediators plays a key role in the pathogenesis and treatment of inflammatory bowel disease. Glutamine can modulate cytokine production by intestinal mucosa in healthy subjects, but studies in inflammatory states are still limited. The aim of this work was to evaluate the effects of glutamine on IL-1beta-induced cytokine production by human gut. METHODS: Duodenal biopsies from healthy volunteers were stimulated in vitro by IL-1beta in the presence of increasing glutamine concentrations. Cytokine production was assessed in culture media by ELISA and cytokine mRNA expression in biopsies by RT-PCR. Results, in pg/mg of tissue, (median [range]), were compared by non-parametric paired tests. RESULTS: IL-1beta stimulation increased IL-6 and IL-8, but did not affect IL-4 and IL-10 production. IL-8 and IL-6 production from stimulated biopsies significantly decreased with increasing glutamine concentration from 0.5 to 10mM, (2543 [828-3634] to 1499 [282-2617] for IL-8, 62 [22-117] to 24 [12-99] for IL-6, both P<0.05), whereas IL-10 production was increased (0.7 [0.2-1.6] to 1.2 [2.6-0.5],P<0.05). Glutamine also increased IL-10 mRNA level in biopsies (P<0.05). IL-4 production was not affected by glutamine. CONCLUSIONS: Glutamine was shown in human intestinal mucosa to reduce the production of the pro-inflammatory cytokines IL-6 and IL-8, and enhance the production of the anti-inflammatory cytokine, IL-10.     

Lymphocyte activation in silica-exposed workers

Exposure to silica dust has been examined as a possible risk factor for autoimmune diseases, including systemic sclerosis, rheumatoid arthritis, systemic lupus erythematosus and ANCA-associated vasculitis. However, the underlying cellular and molecular mechanisms resulting in the increased prevalence of autoimmunity remain elusive. To clarify these mechanisms, we studied various markers of immune activation in individuals occupationally exposed to silica dust, i.e., serum levels of soluble IL-2 receptor (sIL-2R), levels of IL-2, other pro- and anti-inflammatory cytokines and lymphoproliferation. Our results demonstrate that silica-exposed individuals present important alterations in their immune response when compared to controls, as shown by increased serum sIL-2R levels, decreased production of IL-2 and increased levels of the pro-inflammatory (IFN-γ, IL-1α, TNF-α, IL-6) as well as anti-inflammatory (IL-10 and TGF-β) cytokines. Furthermore, silica-exposed individuals presented enhanced lymphoproliferative responses. Our findings provide evidence that the maintenance of immune homeostasis may be disturbed in silica-exposed individuals, possibly resulting in autoimmune disorders.     

Modulation of nitric oxide and cytokines production by L-arginine in human gut mucosa

BACKGROUND: Arginine is a conditionally essential amino-acid with immuno-modulatory properties, mainly through the nitric oxide (NO) pathway. AIM: To assess the effects of arginine on intestinal production of pro- and anti-inflammatory cytokines and NO in human gut. METHODS: An enteral solution of arginine or a control solution of amino-acids was administered to 8 healthy volunteers on a randomized cross-over design. Duodenal biopsies were taken. Pro- (IL-6, IL-8) and anti-inflammatory (IL-4, IL-10) cytokines mRNA expression was assessed by RT-PCR. Other biopsies were cultured with 0.1, 0.5 or 2 mM arginine or control amino-acids, under basal or IL-1beta-induced inflammatory conditions. Interleukin-4, IL-6, IL-8 and IL-10 production was measured in culture supernatant by ELISA and NO production by Griess reaction. RESULTS: Arginine enhanced the production of NO under inflammatory conditions in a dose-dependent manner (P=0.03). IL-1beta increased the production of IL-8 and IL-6 (P<0.01). Arginine had no effect on pro- and anti-inflammatory cytokines production both under basal and inflammatory conditions. CONCLUSIONS: Arginine enhanced the production of NO but did not affect that of cytokines in inflammatory human gut. Further clinical studies are required to assess whether arginine-enhanced NO production plays a beneficial or deleterious effect in intestinal inflammation.     

2,5-dihydroxyacetophenone isolated from Rehmanniae Radix Preparata inhibits inflammatory responses in lipopolysaccharide-stimulated RAW264.7 macrophages

Rehmanniae Radix Preparata, the steamed root of Rehmannia glutinosa Libosch, has been widely used for the treatment of inflammatory conditions in Oriental medicines. In this study we evaluated the effects of 2,5-dihydroxyacetophenone (DHAP) isolated from Rehmanniae Radix Preparata on inflammatory responses in lipopolysaccharide (LPS)-stimulated RAW264.7 mouse macrophages. LPS-stimulated RAW264.7 cells were used to investigate the anti-inflammatory activity of DHAP on the production of inflammatory mediators such as nitric oxide (NO), inducible NO synthase (iNOS), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6. DHAP significantly inhibited NO production via the suppression of iNOS expression and significantly decreased levels of the pro-inflammatory cytokines TNF-α and IL-6 via the down-regulation of their mRNA expression in LPS-stimulated RAW264.7 cells. DHAP potently inhibited the phosphorylation of extracellular signal-related kinase (ERK) 1/2 and the nuclear translocation of nuclear factor-κB (NF-κB) p65 in LPS-stimulated cells. These results indicate that DHAP inhibits the production of inflammatory mediators in activated macrophages by blocking the ERK1/2 and NF-κB signaling pathways. Our results suggest that DHAP from Rehmanniae Radix Preparata has anti-inflammatory activity in activated macrophages, raising the possibility that this compound has a therapeutic potential for inflammatory conditions.     

Investigation into the role of the cholinergic system in radiation-induced damage in the rat liver and ileum

It has been previously shown that acetylcholine (ACh) may affect pro-inflammatory and anti-inflammatory cytokines. The role of the cholinergic system in radiation-induced inflammatory responses and tissue damage remains unclear. Therefore, the present study was designed to determine the radio-protective properties of the cholinergic system in the ileum and the liver of rats. Rats were exposed to 8-Gy single-fraction whole-abdominal irradiation and were then decapitated at either 36 h or 10 d post-irradiation. The rats were treated either with intraperitoneal physiological saline (1 ml/kg), physostigmine (80 µg/kg) or atropine (50 μg/kg) twice daily for 36 h or 10 d. Cardiac blood samples and liver and ileal tissues were obtained in which TNF-α, IL-1β and IL-10 levels were assayed using ELISA. In the liver and ileal homogenates, caspase-3 immunoblots were performed and myeloperoxidase (MPO) activity was analyzed. Plasma levels of IL-1β and TNF-α increased significantly following radiation (P < 0.01 and P < 0.001, respectively) as compared with non-irradiated controls, and physostigmine treatment prevented the increase in the pro-inflammatory cytokines (P < 0.01 and P < 0.001, respectively). Plasma IL-10 levels were not found to be significantly changed following radiation, whereas physostigmine augmented IL-10 levels during the late phase (P < 0.01). In the liver and ileum homogenates, IL-1β and TNF-α levels were also elevated following radiation, and this effect was inhibited by physostigmine treatment but not by atropine. Similarly, physostigmine also reversed the changes in MPO activity and in the caspase-3 levels in the liver and ileum. Histological examination revealed related changes. Physostigmine experiments suggested that ACh has a radio-protective effect not involving the muscarinic receptors.     

Gene expression profiling in naïve and vaccinated rainbow trout after Yersinia ruckeri infection: insights into the mechanisms of protection seen in vaccinated fish

Despite the importance and success of vaccination against bacterial diseases in fish, little is known about the mechanisms of vaccine-induced disease resistance. In this study a known efficacious bacterial vaccine, to Enteric Redmouth Disease (ERM), was used to vaccinate rainbow trout, and sixty days later the fish were challenged with the causative agent of the disease, Yersinia ruckeri. The bacterial burden in the spleen, the spleen index, and the expression profiles of pro- and anti-inflammatory cytokines and marker genes for T helper (Th) cells in the spleen and gills were analyzed, in comparison to the profiles in naïve/challenged fish. As expected, the bacterial burden in the spleen of naïve fish increased over time and was correlated with the spleen index after Y. ruckeri challenge. The gene expression data showed that pro-inflammatory cytokines were upregulated post-infection in the spleen of both naïve and vaccinated fish after Y. ruckeri challenge although the pro-inflammatory cytokine expression was much lower in vaccinated fish compared to the naïve fish. A correlated expression between pro-inflammatory cytokines and anti-inflammatory cytokines was only seen in spleen of ERM vaccinated fish, where a Th1-like response was indicated by the correlated gene expression of IFN-γ, T-bet and IL-2. In contrast, in the gills, the inflammatory gene response was enhanced in vaccinated fish compared to naïve fish, but perhaps more importantly there was a strong upregulation of IL-22 which was negatively correlated with IFN-γ gene expression at this site. Thus, it is possible that different types of adaptive responses are on-going within the vaccinated fish during infection with Y. ruckeri, potentially affected by the site and stage of infection.