Inter-ictal assay of peripheral circulating inflammatory mediators in migraine patients under adjunctive cervical non-invasive vagus nerve stimulation (nVNS): A proof-of-concept study

Objective

To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs.

调节性B淋巴细胞在视神经脊髓炎谱系疾病患者外周血中的表达和意义

背景 调节性B淋巴细胞(Breg)是一类具有负向免疫调节作用的细胞,在多种自身免疫性疾病中表达异常,视神经脊髓炎谱系疾病(NMOSD)系自身免疫性疾病,目前关于Breg在NMOSD患者外周血中的表达和意义的研究较少。目的 研究Breg在NMOSD患者外周血中的表达和意义。方法 选取2019年6月—2021年12月新疆医科大学第一附属医院神经内科收治的NMOSD患者55例作为NMOSD组,选取同期本院体检正常的健康志愿者50例作为对照组。运用流式细胞仪检测两组研究对象外周血中CD19⁺CD24^hiCD38^hi Breg、CD19⁺CD24^hiCD27⁺Breg的表达。采用酶联免疫吸附测定(ELISA)法检测和比较两组研究对象血清中白介素10(IL-10)、白介素35(IL-35)和转化生长因子β1(TGF-β1)的水平。结果 NMOSD组患者CD19⁺CD24^hiCD38^hi Breg、CD1...     

巴豆醛致雄性大鼠神经毒性作用的研究

目的探讨巴豆醛暴露致雄性大鼠神经毒性作用,分析其可能的作用机制。方法于2019年7至10月,将24只SPF级雄性Wistar大鼠随机分为对照组和2.5、4.5、8.5 mg/kg染毒组,每组6只,分别经口给予0.0、2.5、4.5、8.5 mg/kg体重巴豆醛溶液,每周5次,连续染毒90 d。染毒结束后,测量大鼠体重,麻醉解剖取大鼠大脑组织和肝组织。测定大脑组织乙酰胆碱酯酶(AChE)活力及肝组织乙酰胆碱(ACh)水平;检测大脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力以及丙二醛(MDA)和还原型谷胱甘肽(GSH)水平;酶联免疫吸附测定(ELISA)法检测大脑组织中白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平。结果与对照组比较,2.5、4.5、8.5 mg/kg染毒组大鼠大脑组织中AChE活力明显降低,8.5 mg/kg染毒组大鼠肝组织中ACh水平明显升高,差异均有统计学意义(P<0.05);与对照组比较,4.5、8.5 mg/kg染毒组大鼠大脑组织中MDA水平明显升高,GSH水平和SOD、GSH-Px活力明显降低,差异均有统计学意义(P<0.05);与对照组比较,2.5、4.5、8.5 mg/kg染毒组大鼠大脑组织中TNF-α、IL-6水平明显升高,4.5、8.5 mg/kg染毒组IL-1β水平明显升高,差异均有统计学意义(P<0.05)。结论巴豆醛暴露可致大鼠神经系统损伤,可能与氧化平衡状态改变及上调大脑组织炎性因子表达等作用有关。     

Tumor-associated lymphocytes (TAL) are competent to produce higher levels of cytokines in neoplastic pleural and peritoneal effusions than those found in sera and are able to release into culture higher levels of IL-2 and IL-6 than those released by PBMC

This work was designed to study the proliferative response of tumor-associated lymphocytes (TAL) from neoplastic effusions against autologous tumor cells and the immunophenotype pattern of TAL from neoplastic effusions and that of PBMC of the same patients. We also compared the serum levels of the cytokines interleukin (IL) 1, 2 and 6, tumor necrosis factor- (TNF) and soluble IL-2 receptor (sIL-2R) with those present in neoplastic effusions of the same patients. Moreover, we examined the ability of TAL and peripheral blood mononuclear cells (PBMC) to produce and release the cytokines and sIL-2R and to express membrane CD25 following their stimulation with phytohemagglutinin (PHA) in vitro. Finally, we compared the cytokines/sIL-2R production and membrane CD25 expression by PHA-stimulated PBMC of the patients with neoplastic effusions with a series of 90 cancer patients without neoplastic effusions and 20 normal healthy subjects. Thirteen neoplastic pleural and eight peritoneal effusions were collected from 11 patients with primary lung cancer, 7 with primary epithelial ovarian cancer, 1 with breast cancer, 1 with pleural mesothelioma, and 1 with pancreatic cancer. The proliferative response of TAL from neoplastic effusions against autologous tumor cells was lower than the response to PHA, IL-2, and anti-CD3, but significant. The percentage distribution of CD3⁺ and CD8⁺ lymphocyte subpopulations was higher in peritoneal than in pleural effusions, while the CD16⁺ subset was higher in pleural than in peritoneal effusions. The percentage distribution of CD16⁺ was significantly lower in pleural effusions than in PBMC of patients with pleural effusions. The CD39 antigen was higher on TAL from peritoneal effusions than on PBMC of the same patients. The levels of IL-1 and sIL-2R in peritoneal effusions did not differ from those measured in the sera of the same patients, while the levels of IL-2, IL-6, and TNF were higher in the peritoneal effusions. The levels of IL-2, IL-6, TNF, and sIL-2R, but not IL-1, in pleural effusions were significantly higher than those found in the sera of the same patients. The amounts of IL-2 and IL-6 produced by TAL were generally higher than those released by PBMC. The secretion of cytokines IL-1, IL-2, and sIL2R by PHA-stimulated PBMC was lower, but IL-1 and IL-6 secretion was higher in cancer patients with neoplastic effusions than in either cancer patients without neoplastic effusions or normal subjects. The CD25 expression on PHA-stimulated PBMC derived from cancer patients with neoplastic effusions was in the same range as that of cancer patients without neoplastic effusions and normal subjects. These findings suggest that TAL may be able to produce cytokines and may be amenable to immune manipulation.Abbreviations FITC Fluorescein-isothiocyanate - IL Interleukin - mAb Monoclonal antibody - MHC Major histocompatibility complex - NK Natural killer - PBMC Peripheral blood mononuclear cells - PHA Phytohemagglutinin - TAL Tumor-associated lymphocytes - TIL Tumor-infiltrating lymphocytes - TNF Tumor necrosis factor- - sIL-2R Soluble interleukin-2 receptor     

The exposure of healthy volunteers to 200 ppm 1,1,1-trichloroethane increases the concentration of proinflammatory cytokines in nasal secretions

Objectives: Irritating effects of organic solvents have usually been measured by means of questionnaires. The aim of the present study was to evaluate the sensitivity of different methods of detecting subclinical irritating effects. Methods: Twelve healthy, non-smoking students were exposed to 200 ppm and to 20 ppm 1,1,1-trichloroethane in an exposure chamber, using a crossover design. The amounts of interleukins (IL)-1β, IL-6 and IL-8 and prostaglandin E₂ (PGE₂) in nasal secretions were measured. Mucociliary transport time was determined with the saccharine test. Ciliary beat frequency of nasal epithelial cells was measured with video-interference contrast microscopy. Subjective symptoms were assessed by questionnaire. Results: Concentrations of ILs were significantly elevated after exposure to 200 ppm 1,1,1-trichloroethane (IL-1β 82.4 vs. 28.8 pg/ml (medians), P=0.003; IL-6 12.2 vs. 7.2 pg/ml, P=0.01; IL-8 549 vs. 424 pg/ml, P=0.007), whereas the other parameters remained unchanged. Conclusion: The interleukins measured proved to be sensitive indicators of irritating effects of 1,1,1-trichloroethane. The German threshold limit (MAK value) of 200 ppm 1,1,1-trichloroethane does not prevent the subclinical inflammation of nasal mucosa. Received: 3 March 1999 / Accepted: 14 June 1999     

Systemic liberation of interleukin-1β and interleukin-1 receptor antagonist in the perioperative phase of liver transplantation

We measured systemic serum levels of interleukin-1 receptor antagonist (IL-1ra), interleukin-1 (IL-1), tumor necrosis factor (TNF-), and interleukin-6 (IL-6) during the preoperative, anhepatic, and postreperfusional phases up to the 7th postoperative day in 60 patients undergoing orthotopic liver transplantation (LTx). In contrast to IL-1, IL-1ra, TNF-, and IL-6 showed a significant elevation in relation to the early phase after reperfusion, while TNF- displayed a high grade of scatter. In addition, IL-1ra levels were significantly elevated during the anhepatic phase. Maximum serum levels were found at 15 min after reperfusion, 120 min after reperfusion, and on the 1st postoperative day, respectively. Serum levels decreased considerably at 24 h and 7 days after reperfusion. The comparative monitoring of systemic cytokine and cytokine antagonist levels, in particular the liberation of IL-1ra and IL-6 may provide useful parameters for the development of new liver preservation theories for LTx.     

Silver serum levels in burned patients treated with silver sulfadiazine and its toxicity on inflammatory cells

BackgroundSilver sulfadiazine (SSD) has been widely used in burned patients for the prevention of local infections. To be biologically active and exert antimicrobial properties, silver needs to be present in the form of silver ions (Ag¹⁺) that bind to negatively charged proteins, namely, the RNA and DNA in microorganisms. However, previous published studies conducted with SSD in the 1990s reported a high level of silver absorption through damaged skin and noted the potential cytotoxicity of Ag¹⁺ to human cells. SSD toxicity, however, had been described in cell cultures using arbitrary silver concentrations. In the present study, we determined the serum silver levels in burned patients treated with SSD and, taking into account the molar Ag¹⁺ concentrations found in these patients, we evaluated the Ag¹⁺ toxicity effects on inflammatory cells (ROS and cytokine production) in vitro.MethodsTwenty patients with an average burned body surface area of 27.68% were included in this study.ResultsPatients’ Ag¹⁺ serum levels reached up to 558 times those of the unexposed controls. Ag¹⁺ was then added to inflammatory cells in vitro at levels up to 2000 times the level of the control, and there was no effect on the viability of the cells nor on the rate of apoptosis. We observed a decrease in reactive oxygen species production by mononuclear (MN) and polymorphonuclear (PMN) cells, as well as a substantial decrease in cytokines IL-1β, IL-6, IL-8, IL-10, and TNF-α production by leukocytes (MN and PNM).ConclusionThese findings suggest that Ag¹⁺ may contribute to negative outcomes after burns, decreasing the primary defense mechanism (respiratory burst) and altering cytokine production.     

细胞因子与老年重症肺部感染病原菌的关系探讨

目的 探讨细胞因子与老年人重症肺部感染病原菌的关系。方法 对20例健康老年人、79例ICU感染早期、感染控制后的老年重症肺部感染患者空腹采血，酶联免疫吸附（ELISA）法测定样本的白细胞介素2受体（IL-2R）、白细胞介素6（IL-6）、白细胞介素8（IL-8）、肿瘤坏死因子α（TNF-α）及C反应蛋白（CRP）的含量，并行冷凝集试验（CAT）排除支原体感染；同时细菌培养明确病原菌，评价细胞因子与老年重症肺部感染病原菌的关系。结果 血清IL-2R、IL-6、CRP水平革兰阴性菌（G^-）感染组、革兰阳性菌（G^-）感染组、真菌感染组分别为较对照组均明显增高（P〈0．01），差异有统计学意义；而感染组间比较差异无统计学意义（P〉0．05）。G^＋感染组的血清IL-8水平明显低于G^-感染组及真菌感染组（P〈0．01），但与对照组比较，差异无统计学意义（P〉0．05）。G^＋感染组血清TNF-α水平较对照组增高（P〈0．05），但不如G^-感染组、真菌感染组较对照组增高明显（P〈0．01）；G^＋感染组血清TNF-α水平与G^-感染组、真菌感染组比较显著低下（P〈0．05）。结论 老年重症肺部G^＋感染者血清IL-2R、IL-6、CRP显著升高，而TNF-α升高较轻，IL-8降低，G^-感染患者、真菌感染患者血清TNF-α、IL-2R、IL-6、IL-8、CRP均显著升高。老年肺部感染初期血清TNF-α、IL-8水平可以做为早期协助预测病原菌的指标。     

缬沙坦对心力衰竭患者血浆细胞因子浓度的影响

目的 :探讨重度充血性心力衰竭 (CHF)患者血浆中细胞因子浓度的变化及其对缬沙坦干预的反应。方法 :选择CHF患者 80例 (CHF组 )和健康体检者 4 0例 (对照组 ) ,采用放免法测定血浆肿瘤坏死因子 (TNF α)、白细胞介素 1(IL 1)和白细胞介素 6 (IL 6 )的浓度 ;然后将CHF组随机分为常规治疗组和加用缬沙坦组各 4 0例 ,1个月后再测定上述指标。结果 :CHF组 3种细胞因子浓度均高于对照组 (P <0 .0 1) ;CHF越重 ,细胞因子的浓度越高 (P <0 .0 1) ;不同病种所致同级CHF的细胞因子浓度无明显差别 (P >0 .0 5 ) ;缬沙坦能改善心功能 ,降低上述细胞因子的浓度 (P <0 .0 1)。结论 :细胞因子在重度CHF的发展中起重要作用 ,而且与基础病无关 ;缬沙坦在改善心功能的同时 ,也降低细胞因子的血浆浓度。