Modified myeloid dendritic cells act as regulatory dendritic cells to induce anergic and regulatory T cells

To exploit a novel strategy to regulate T cell-mediated immunity, we established human and murine modified dendritic cells (DCs) with potent immunoregulatory properties (designed as regulatory DCs), which displayed moderately high expression levels of major histocompatibility complex (MHC) molecules and extremely low levels of costimulatory molecules compared with their normal counterparts. Unlike human normal DCs, which caused the activation of allogeneic CD4(+) and CD8(+) T cells, human regulatory DCs not only induced their anergic state but also generated CD4(+) or CD8(+) regulatory T (Tr) cells from their respective naive subsets in vitro. Although murine normal DCs activated human xenoreactive T cells in vitro, murine regulatory DCs induced their hyporesponsiveness. Furthermore, transplantation of the primed human T cells with murine normal DCs into severe combined immunodeficient (SCID) mice enhanced the lethality caused by xenogeneic graft-versus-host disease (XGVHD), whereas transplantation of the primed human T cells with murine regulatory DCs impaired their ability to cause XGVHD. In addition, a single injection of murine regulatory DCs following xenogeneic or allogeneic transplantation protected the recipients from the lethality caused by XGVHD as well as allogeneic acute GVHD. Thus, the modulation of T cell-mediated immunity by regulatory DCs provides a novel therapeutic approach for immunopathogenic diseases.     

Intravascular lymphomatosis presenting as systemic inflammatory response syndrome

Intravascular lymphomatosis is an unusual form of non-Hodgkin lymphoma characterized by intravascular proliferation of atypical lymphoid cells in multiple organs. It can cause systemic inflammatory response syndrome due to primary release of cytokines by the tumor cells or secondary release of cytokines after vascular occlusion by the tumor cells. It is a potentially fatal condition, because multiorgan failure can ensue due to thrombotic vascular occlusion. This is a very rare condition and most cases are diagnosed post mortem. We present a case of systemic inflammatory response syndrome and subsequent death from multiorgan failure in a patient with intravascular lymphoma.     

The systemic inflammatory response syndrome correction in acute destructive pancreatitis

Acute pancreatitis is a disease of variable severity. In which some patients experience mild, self-limited attacks while others manifest a severe, highly morbid, and frequently lethal attack. The exact mechanisms by which diverse etiological factors induce an attack are still unclear. Recent studies have established the role played by inflammatory mediators in the pathogenesis of acute pancreatitis. In our research we have estimated influence of not steroid anti-inflammatory preparation on synthesis pro-and anti-inflammatory Cytokines at healthy donors and at patients with Acute pancreatitis.     

Sorbents in acute renal failure and the systemic inflammatory response syndrome

Renal replacement therapy in acute renal failure is currently focused on the use of modifications of dialysis (continuous arteriovenous hemofiltration and hemodiafiltration) to remove middle molecular weight toxins, consisting of small proteins, and cytokines involved in the systemic inflammatory response syndrome (SIRS). Conventional high-flux dialyzers are not efficient at removing these molecules, prompting the investigation of sorbents to augment or replace dialysis. Sorbents have been developed to modulate SIRS by targeting cytokines such as IL-1, IL-6, IL-10, IL-18 and TNF, among others. Extensive pre-clinical studies are underway to demonstrate the clinical utility and safety of either adding sorbent hemoadsorption devices to hemodialysis, or the use of such devices alone in SIRS, sepsis, acute renal failure, cardiopulmonary bypass and end-stage renal disease.     

急性缺血性卒中患者全身性炎症反应综合征的预测因素

目的：探讨急性缺血性卒中患者发生全身性炎症反应综合征(systemic inflammatory response syndrome, SIRS)的预测因素。方法纳入2010年1月至2014年4月期间住院的急性缺血性卒中患者,并收集两组人口统计学、血管危险因素、基线临床资料和实验室检查结果。采用流式细胞术分析外周血辅助性 T 细胞(T helper cel , Th)亚群。采用双抗体夹心法酶联免疫吸附试验检测外周血干扰素-γ(interferon-γ, IFN-γ)和白细胞介素-4(interleukin-4, IL-4)水平。结果共纳入143例急性缺血性卒中患者,SIRS 组56例,非 SIRS 组87例。单变量分析显示,2组患者在高血压史、卒中史、基线收缩压、低密度脂蛋白胆固醇水平、美国国立卫生研究院卒中量表(National Institutes of Health Stroke Scale, NIHSS)评分、Th1细胞百分比和 IFN-γ浓度方面差异有统计学意义(P 均<0．05)。多变量 logistic 回归分析显示, NIHSS 评分≥6分[优势比( odds ratio, OR)2．40,95%可信区间(confidence interval, CI)1．24~5．15;P =0．008]、Th1细胞百分比降低(OR 2．81,95% CI 1．51~6．83;P =0．013)和 INF-γ浓度下降(OR 4．63,95% CI 1．01~9．72;P =0．004)是急性缺血性卒中患者发生SIRS 的独立预测因素。结论神经功能缺损严重、Th1细胞百分比下降或 IFN-γ水平下降会增高急性缺血性卒中患者伴发 SIRS 的风险。     

Propolis derivatives inhibit the systemic inflammatory response and protect hepatic and neuronal cells in acute septic shock

BackgroundSevere pathogenic infection triggers excessive release of cytokines as part of the massive inflammatory response associated with septic shock.ObjectivesTo investigate the protective effect of caffeic acid phenethye ester (CAPE) against lipopolysaccharide (LPS) induced endotoxemia, hepatic and neuronal damage and the associated systemic inflammatory response (SIR).MethodsFifty male Wister rats were divided into: control, LPS, and CAPE+LPS groups. Plasma concentrations of various cytokines, including TNF-α, IL-1α, IL-1β, IL-6, IL-4, IL-10, and sICAM-1 were evaluated. In addition, the histopathological changes in the hepatic and neural cells were assessed.ResultsThe LPS group showed high inflammatory cytokines and sICAM-1 levels reflecting the presence of SIR. Hepatocyte necrosis, apoptosis, extensive hemorrhage and inflammatory cellular infiltration together with brain astrocytes swelling, early neuron injury and presence of inflammatory foci confirmed the toxic tissue damage. Use of CAPE decreased the inflammatory cytokines and increased the anti-inflammatory cytokines levels. This biochemical evidence of decreased SIR was confirmed histologically by decreased cellular infiltration in the liver and brain tissue which coincides with preserved structure and protection of the liver and brain cells from the toxic effects of LPS.ConclusionThe ability of CAPE to alleviate the SIR, hepatic and neuronal cell damage induced by LPS and galactosamine could be attributed to its ability to reverse the imbalance of the pro- and anti-inflammatory cytokines which may lead to the inhibition of adhesion molecules’ expression. CAPE is a promising agent that could help in the prophylaxis and treatment of septic shock.     

肠内免疫微生态营养对急性坏死性胰腺炎全身炎症反应影响的研究

目的 探讨肠内免疫微生态营养对ANP猪全身炎症反应的影响.方法 胰管注射5%牛磺胆酸钠1ml/kg体重制备猪ANP模型.造模后24 h,18头猪按随机分组法分为胃肠外营养组(PN)、肠内要素营养组(EN)和肠内免疫微生态营养组(EIN),分别进行相应的营养支持8 d.造模前、造模后24 h、营养支持1 d、2 d、4 d、8 d分别检测外周血内毒素、TNF-α、IL-1β、IL-6、IL-10及单核细胞NF-κB活性.8 d时取胰腺行病理学检查.结果 胰腺病理改变符合ANP.造模后24 h,EIN组外周血内毒素、TNF-α、IL-1β、IL-6、IL-10和单核细胞NF-κB水平分别为(1.85±0.18)EU/L、(461.59±128.25)pg/ml、(185.49±58.81)pg/ml、(354.26±34.63)pg/ml、(110.32±25.18)pg/ml、(51.06 ±2.27)%,均较造模前明显增高(P＜0.01),但与其他两组无显著差异;营养支持8 d后,EIN组血浆上述各项分别为(1.48±0.16)EU/L、(30.11±9.12)pg/ml、(20.17±7.04)pg/ml、(36.42±7.24)pg/ml、(89.46±13.54)pg/ml、(9.06±0.17)%,均较EN组、PN组明显下降(P＜0.05),且IL-10/IL-6比值为2.51±0.42,与制模前的2.28±0.19接近.结论 早期肠内免疫微生态营养能有效减轻内毒素血症,降低NF-κB活性及细胞因子浓度,维持促抗炎反应平衡.     

慢性阻塞性肺疾病患者急性加重期饮食摄入与血清瘦素及全身炎症状态关系的研究

目的研究慢性阻塞性肺疾病(COPD)患者急性加重期饮食摄入与血清瘦素水平及全身炎症状态的相关关系,探讨血清瘦素和全身炎症在COPD营养不良发生中的作用。方法观察40例COPD急性加重期患者治疗前,治疗第7天、第12天的饮食摄入量、血清瘦素及可溶性肿瘤坏死因子受体(sTNFR)的水平变化;测定患者治疗第12天的营养状态参数。12例正常健康者的血清瘦素、sTNFR水平作为正常对照。分析各参数相关性。用酶联免疫吸附试验(ELISA)测定血清瘦素、sTNFR水平,饮食摄入量由24小时膳食记录,经营养分析软件计算获得。结果①患者治疗前饮食摄入量低于日常习惯饮食,随着治疗时间的延长,饮食摄入量逐渐恢复至日常水平。在治疗第7天,饮食摄入量与瘦素的自然对数、sTNFR55均呈显著负相关(r=-0.536,P<0.01;r=-0.729,P<0.001);治疗第12天此相关关系仍存在。②治疗第7天和第12天,排除体重指数(BMI)影响后,血清瘦素与sTNFR55均呈显著正相关(r=0.53,P<0.05;r=0.512,P<0.05)。③治疗第12天,血清瘦素与BMI、理想体重百分比、三头肌皮皱厚度、肩胛下皮皱厚度、上臂中部周径等营养参数均呈显著正相关(P均<0.05)。结论COPD患者急性加重期存在短暂的饮食摄入减少,这与提高的血清瘦素水平及全身炎症反应有关。“细胞因子瘦素”作用机制可能参与了COPD营养不良的发生。     

Regulatory T cells and toll-like receptors: regulating the regulators

Regulatory T cells (Treg) play a crucial role in maintaining control of leucocytes. Several studies have shown that in vivo Treg depletion results in autoimmune syndromes like thyroiditis, gastritis, diabetes mellitus and colitis, but at the same time, may also result in improved anti-tumour vaccination. Although Treg are recognised to maintain peripheral tolerance in healthy individuals, recent research has shown that Treg also suppress immune responses during infections to prevent tissue damage. How the Treg themselves are regulated is still under investigation. Their suppressive activity must be regulated in order to allow for the effective elimination of pathogens. Until recently, this control of Treg function was found to be through modulation via cytokines or by stimulation via co-stimulatory molecules on antigen-presenting cells. It is now demonstrated, however, that the presence of pathogens can be communicated to Treg directly through toll-like receptors (TLRs). Up until now, Treg have been reported to respond to ligands for TLR2, 4, 5 and 8, and different TLRs can have alternative effects on Treg resulting in more suppression or, in contrast, abrogation of suppression. As TLRs can also recognise endogenous proteins, such as heat shock proteins, it is tempting to speculate on the role of these proteins in modulating Treg function during chronic inflammation. In this review, we will discuss the implications of TLR engagement on Treg and any consequences this may have for chronic autoinflammatory diseases like rheumatoid arthritis (RA).     

调节性T细胞与炎症性肠病

炎症性肠病(IBD)的病因和发病机制尚未完全明确,肠道黏膜免疫系统对肠道非致病抗原的异常反应所导致的炎症过程在发病中起重要作用.调节性T细胞(Treg)有抑制自身免疫的功能,是维持肠道免疫稳态的重要因素.Treg功能紊乱致免疫耐受被打破可能是导致人类IBD的原因之一.此文就目前国内外关于Treg在IBD的发病机制中的研...     

调节性B细胞与炎症性肠病

B细胞能够针对自身抗原产生相应的抗体,在自身免疫性疾病的发生和发展中发挥重要的作用.近年来的研究发现部分B细胞具有调节功能,这部分B细胞被命名为调节性B细胞,调节性B细胞可以分泌白细胞介素-10、转移生长因子-β1等细胞因子,中和病理性T细胞,或是直接与其它免疫细胞结合,抑制免疫应答.此综述初步探讨调节性B细胞在炎症性肠病中的作用及其可能机制.     

调节性T细胞与炎症性肠病

炎症性肠病(IBD)包括溃疡性结肠炎(UC)和克罗恩病(CD),是一种病因和发病机制尚未完全明确的肠道疾病。肠黏膜免疫调节细胞和多种细胞因子参与免疫反应和炎症过程,免疫功能紊乱和免疫耐受异常是导致其发病的主要因素。此文就调节性T细胞与IBD的研究进展作一综述。     

Supplemental oxygen therapy does not affect the systemic inflammatory response to acute myocardial infarction

Background

Oxygen therapy has been used routinely in normoxemic patients with suspected acute myocardial infarction (AMI ) despite limited evidence supporting a beneficial effect. AMI is associated with a systemic inflammation. Here, we hypothesized that the inflammatory response to AMI is potentiated by oxygen therapy.

Methods

The DET ermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO 2X‐AMI ) multicentre trial randomized patients with suspected AMI to receive oxygen at 6 L min^?1 for 6–12 h or ambient air. For this prespecified subgroup analysis, we recruited patients with confirmed AMI from two sites for evaluation of inflammatory biomarkers at randomization and 5–7 h later. Ninety‐two inflammatory biomarkers were analysed using proximity extension assay technology, to evaluate the effect of oxygen on the systemic inflammatory response to AMI .

Results

Plasma from 144 AMI patients was analysed whereof 76 (53%) were randomized to oxygen and 68 (47%) to air. Eight biomarkers showed a significant increase, whereas 13 were decreased 5–7 h after randomization. The inflammatory response did not differ between the two treatment groups neither did plasma troponin T levels. After adjustment for increase in troponin T over time, age and sex, the release of inflammation‐related biomarkers was still similar in the groups.

Conclusions

In a randomized controlled setting of normoxemic patients with AMI , the use of supplemental oxygen did not have any significant impact on the early release of systemic inflammatory markers.

     

Monitoring of serum proteinase-antiproteinase balance and systemic inflammatory response in prognostic evaluation of acute pancreatitis

With the aim of studying the clinical usefulness and applicability of circulating levels of protease inhibitors, complement factors, acute phase reactants, and leukocytic enzymes in the prognostic evaluation of acute pancreatitis (AP), the present prospective multicenter study has been carried out. A total of 182 patients with AP have been included, to whom an exhaustive evolutive protocol has been applied from the time of their hospital admission (2–12 hr from the onset of the disease) until the 15th day of evolution in order to clearly define them. The severe episodes exhibit a greater consumption of α₂-macroglobulin, and C3 and C4 complement factors, as well as a greater increase of α₁-protease inhibitor, C-reactive protein and polymorphonuclear elastase than mild events, with regards to the underlying pathophysiological condition. The determination of the plasma levels of leukocytic elastase in the first hours of evolution allows a prediction of the severity of the acute pancreatitis event with a high reliability (predictive values that become higher than 90%). The clinical value of the remaining parameters analyzed, in this aspect, is less, being applicable to the monitoring of the disease.     

Modulation of systemic inflammatory response after cardiac surgery

Cardiac surgery and cardiopulmonary bypass initiate a systemic inflammatory response largely determined by blood contact with foreign surfaces and the activation of complement. It is generally accepted that cardiopulmonary bypass initiates a whole-body inflammatory reaction. The magnitude of this inflammatory reaction varies, but the persistence of any degree of inflammation may be considered potentially harmful to the cardiac patient. The development of strategies to control the inflammatory response following cardiac surgery is currently the focus of considerable research efforts. Diverse techniques including maintenance of hemodynamic stability, minimization of exposure to cardiopulmonary bypass circuitry, and pharmacologic and immunomodulatory agents have been examined in clinical studies. This article briefly reviews the current concepts of the systemic inflammatory response following cardiac surgery, and the various therapeutic strategies being used to modulate this response.