Clinical significance of detecting the serum levels of IFN-γ、IL-10、TGF-β1 in patients with viral hepatitis B

目的 评价乙型病毒性肝炎患者血清IFN-γ、IL-10、TGF-β1水平测定的临床意义.方法 采用酶联免疫吸附法测定70例急、慢性乙型肝炎及肝硬化患者血清IFN-γ、IL-10、TGF-β1水平,并检测肝功能、肝纤维化以及HBV DNA指标;以健康人18例为正常对照组.结果 随着患者病情的加重和肝纤维化的进展,血清IFN-γ水平逐渐下降,而IL-10和TGF-β1水平则逐渐上升.血清IFN-γ水平与TBIL、PCⅢ、CⅣ、HA和LN呈显著负相关,而与ALB和PTA呈显著正相关;血清IL-10水平与TBIL、HA呈显著正相关,而与ALB和PTA呈显著负相关;血清TGF-β1水平与TBIL、PCⅢ、CⅣ、HA和LN呈显著正相关,而与ALB和PTA呈显著负相关(P＜0.01).HBV DNA阳性患者肝纤四项水平显著高于阴性患者(P＜0.05或＜0.01).结论 IFN-γ、IL-10、TGF-β1不仅与肝细胞损伤有良好的相关性,而且与肝纤维化的形成密切相关.因此,测定这些细胞因子水平,在监测慢性乙型肝的发生发展、肝纤维化进展程度以及评价治疗效果及预后具有重要的实用价值.     

反复喘息婴幼儿血清25-羟维生素D3、干扰素-γ(IFN-γ)及IL-4、IL-13水平及相关性研究

目的 研究讨论反复喘息婴幼儿血清25-羟维生素D3、干扰素-γ(IFN-y)、IL-4和IL-13水平及相关性.方法 选取我科2013年3月至2015年3月治疗诊断为反复喘息疾病的婴幼儿,其中喘息发作期患儿、缓解期患儿、同期正常婴幼儿各20例分别设为A组、B组和C组,测定三组婴幼儿血清中25-羟维生素D3、IFN-γ、IL-4及IL-13含量,采用方差分析判断三组各因子含量差异是否有显著性.采用LSD多重分析判断两两各因子是否有显著性差异.采用相关性分析判断各因子之间是否有相关性.结果 三组25-OHV-D3、IFN-γ、IL-4、IL-13含量比较差异均有显著性(F值分别为218.86、197.33、298.10、305.41,p值分别为0.001、0.001、0.000、0.000).IFN-y与IL-4、IL-13呈负相关而与25-OH-VD3呈正相关(r值分别为-0.912、-0.811、0.850).结论 反复喘息婴幼儿血清IL-4、IL-13水平显著性增高,而25-羟维生素D3和干扰素-y水平降低、提示气道炎症与IL-4、IL-13表达升高及25-羟维生素D3、干扰素-y表达降低有关,反复喘息患儿体内存在Th1、Th2失衡情况.     

Changes and their significances of IFN-γ, TNF-α and IL-2 level in mouse peripheral blood following intraperitoneal injection with influenza viruses

Objective To observe changes of IFN-γ, TNF-α and IL-2 levels in mouse peripheral blood following intraperitoneal injection with influenza viruses. Methods Mice were divided into 3 groups randomly and injected with human H3N2 influenza virus, avian H9N2 influenza virus and sterilized virus-free allantoic fluid, respectively. Sera in different groups were collected at several time points after virus injection, and the levels of IFN-γ, TNF-α and IL-2 in peripheral blood were tested by sandwich ELISA. Statistical analysis was made using analysis of variance and LSD-t test. Results The levels of IFN-γ and IL-2 in peripheral blood in influenza viruses injection groups were significantly higher than those in negative control group, and no significant difference in TNF-α level was found between influenza viruses injection groups and negative control group. Conclusion Intraperitoneal injection with human or avian influenza viruses can promote the production of IFN-γ and IL-2 in mouse peripheral blood, but it has little effect on the production of TNF-α.     

Changes and their significances of IFN-γ, TNF-α and IL-2 level in mouse peripheral blood following intraperitoneal injection with influenza viruses

Objective To observe changes of IFN-γ, TNF-α and IL-2 levels in mouse peripheral blood following intraperitoneal injection with influenza viruses. Methods Mice were divided into 3 groups randomly and injected with human H3N2 influenza virus, avian H9N2 influenza virus and sterilized virus-free allantoic fluid, respectively. Sera in different groups were collected at several time points after virus injection, and the levels of IFN-γ, TNF-α and IL-2 in peripheral blood were tested by sandwich ELISA. Statistical analysis was made using analysis of variance and LSD-t test. Results The levels of IFN-γ and IL-2 in peripheral blood in influenza viruses injection groups were significantly higher than those in negative control group, and no significant difference in TNF-α level was found between influenza viruses injection groups and negative control group. Conclusion Intraperitoneal injection with human or avian influenza viruses can promote the production of IFN-γ and IL-2 in mouse peripheral blood, but it has little effect on the production of TNF-α.     

Generation of TNFα, IFNγ, IL-4, IL-6 and IL-10 in Trichinella spiralis infected mice: effect of the anti-inflammatory compound mimosine

The plant amino acid mimosine has been demonstrated to arrest cell cycle progression in the late G1-phase, and inhibits [3H] thymidine incorporation in cultured fibroblasts. In this study, 10 mice were infected with Trichinella spiralis, a nematode parasite, and treated with the antiinflammatory compound L-mimosine to determine if any alteration in the chronic inflammatory state occurred by investigating the host's immunological response. Mimosine was used at 250 g/bolus for 25 days starting five days before the infection and continuing daily for 35 days then TNF, IFN-, IL-4, IL-6, and IL-10 were determined by ELISA method, after 0, 1, 7, 14, 21, 28, 35 days post-infection, in the serum of treated or untreated animals. When animals with T. spiralis were treated with L-mimosine, inhibition of TNF was observed within 21 days post-infection, compared with the controls (untreated mice). IFN was inhibited only up to the 21^st day, while IL-6 was inhibited up to the 7^th day post-infection and the inhibition of IL-4 was seen mainly at 21^st and 35^th day p.i. Mimosine-treated mice did not statistically affect the secretion of IL-10 (p > 0.05). In healthy animals, the production of cytokines were within the same limits compared with those of non-infected animals treated with L-mimosine. Our studies suggest that mimosine proved to be more effective in inhibiting TNF and IL-6, which are mainly produced by macrophages and less effective in inhibiting IL-4, which is produced by T-cells.     

Novel anti-arthritic mechanisms of trans-cinnamaldehyde against complete Freund’s adjuvant-induced arthritis in mice: involvement of NF-кB/TNF-α and IL-6/IL-23/ IL-17 pathways in the immuno-inflammatory responses

Inflammopharmacology - Trans-cinnamaldehyde (TCA), a natural cinnamaldehyde derivative of cinnamon oil, is known for anti-inflammatory, anti-bacterial, anti-fungal, anti-diabetic, and anti-cancer...     

Anti-HIV drugs,lopinavir/ritonavir and atazanavir,modulate innate immune response triggered by Leishmania in macrophages: The role of NF-κB and PPAR-γ

This study evaluated the influence of HIV protease inhibitors lopinavir/ritonavir (LPV/RTV) and atazanavir (ATV) on macrophage functions during their first interaction with Leishmania. Macrophages from BALB/c mice treated for 10 days with LPV/RTV and ATV, infected or not in vitro with L. (L.) amazonensis, were used to investigate the effects of these drugs on infection index, leishmanicidal capacity, cytokine production and PPAR-γ and RelB expression. LPV/RTV and ATV treatments significantly increased the infection index and the percentage of Leishmania-infected macrophages compared to untreated infected macrophages. There was no correlated increase in the production of NO and H₂O₂ leishmanicidal molecules. Promastigotes derived from Leishmania-infected macrophages from LPV/RTV and ATV-treated BALB/c mice had an in vitro growth 45.1% and 56.4% higher in groups treated with LPV/RTV and ATV than with PBS in culture. ATV treatment reduced IL-12p70 and IL-10 secretion in Leishmania-infected macrophages, but had no effect on IL-23 and TNF production. LPV reduced IL-10 and had no effect on IL-12p70, TNF and IL-23 secretion. ATV treatment decreased PPAR-γ expression in Leishmania-infected macrophages compared to untreated infected macrophages. In addition, LPV/RTV, but not ATV, reduced RelB cytoplasm-to-nucleus translocation in Leishmania-infected macrophages. Results showed that LPV/RTV and ATV HIV protease inhibitors were able to modulate innate defense mechanisms against Leishmania via different intracellular pathways. Although HIV protease inhibitors are highly efficient to control the Human Immunodeficiency Virus, these drugs might also influence the course of leishmaniasis in HIV-Leishmania-co-infected individuals.     

Changes in the concentrations of inflammatory and oxidative status biomediators (MIP-1 α, PMN elastase,MDA, and IL-12) in depressed patients with and without posttraumatic stress disorder

Background

Both proinflammatory cytokines and oxidative stress are considered an imbalance between the cellular production of reactive oxygen species and the antioxidant defense mechanisms. An inflammatory response that occurs in depression leads to a synergy between pro-inflammatory cytokines and oxidative stress. This synergy induces common signal transduction pathways that boost the inflammatory cascade. The object of this study was to assess the concentrations of inflammatory and oxidative status biomediators such as MIP-1α, PMN elastase, MDA, and IL-12 in depressed patients with and without posttraumatic stress disorder (PTSD), and with PTSD alone.

Decreased severity of experimental autoimmune encephalomyelitis during resveratrol administration is associated with increased IL-17+IL-10+ T cells,CD4− IFN-γ+ cells,and decreased macrophage IL-6 expression

Experimental autoimmune encephalomyelitis (EAE), an animal model of Multiple Sclerosis, is induced after injection of PLP_139–151 myelin peptide in complete Freund's adjuvant into SJL/J mice. During EAE, T cells and macrophages infiltrate the brain, produce cytokines IL-17, IFN-γ, TNF-α, or IL-6, and bring about autoimmune neuroinflammation. However, infiltrating T cells which simultaneously produce IL-17 and IL-10 or infiltrating CD4⁻ NKT cells that produce IFN-γ protect against EAE. Resveratrol, a plant polyphenol, exhibits anti-inflammatory properties. To determine if resveratrol can relieve EAE, SJL/J mice were administered diets enriched in resveratrol at EAE injection. EAE symptoms were significantly less compared with controls in mice fed resveratrol. At day 56 of EAE, splenic T cells from mice fed 0%, 0.04% or 0.08% resveratrol that were restimulated with PLP_139–151 produced similar levels while splenic T cells from mice fed 0.02% resveratrol produced significantly higher levels of IL-17, IFN-γ, and TNF-α. At peak EAE (day 14), mice fed resveratrol had higher numbers of IL-17⁺ T cells, IL-17⁺/IL-10⁺ T cells, and CD4⁻IFN-γ ⁺ cells in the brain and spleen compared with controls. Adoptive transfer of day 14 EAE encephalogenic T cells into mice fed resveratrol reduced the severity of EAE. In addition, resveratrol directly suppressed expression of IL-6 and IL-12/23 p40 but increased expression of IL-12 p35 and IL-23 p19 from macrophages. Therefore resveratrol protection against EAE is not associated with declines in IL-17⁺ T cells but is associated with rises in IL-17⁺/IL-10⁺ T cells and CD4^-IFN-γ⁺ and with repressed macrophage IL-6 and IL-12/23 p40 expression.     

慢加急(亚急)性肝衰竭动态观察IL-2、IL-4、IL-6、IL-10、IFN-γ、TNF-α的临床意义*

目的：动态观察慢加急(亚急)性肝衰竭(acute on chronic liver failure, ACLF)的IL-2、IL-4、IL-6、IL-10、IFN-γ、TNF-α在不同病程时期（第0周、第8周）变化,对临床病情变化、预后及转归起到一定指导作用。方法：采用酶联免疫吸附法（ELISA）法,检测ACLF组、慢性乙型肝炎组（Chronic Hepatitis B,CHB）、健康对照组的血清,采用ACLF患者入组第0周与治疗后第8周的其他两组进行比较。结果：1.在治疗前（第0周）,ACLF组的IL-2、IL-4、L-6、IL-10、IFN-γ、TNF-α水平均高于CHB、对照组,且差异有统计学意义;且CHB组的IL-4水平高于对照组（p<0.01）;CHB组的IL-6水平高于对照组（p<0.05）;CHB组的IFN-γ水平高于对照组（p<0.05）;CHB组的IFN-γ水平高于对照组（p<0.05）。2. 在ACLF入组经过治疗第8周时,ACLF组的IL-2、IL-4、IL-6、IL-10、IFN-γ、TNF-α水平均有显著下降,但ACLF组IL-2水平仍高于CHB、对照组（p<0.05,p<0.01）ACLF组IL-4水平仍高于CHB组、对照组（p<0.01）,且CHB组IL-4水平高于对照组（p<0.01）;ACLF组IL-6水平高于CHB组、对照组（p<0.01）,且CHB组IL-6水平高于对照组;ACLF组IL-10水平高于对照组（p<0.01）;ACLF组IFN-γ水平高于CHB组、对照组（p<0.05、p<0.01）;ACLF组TNF-α水平高于对照组（p<0.01）,CHB组TNF-α水平高于对照组（p<0.05）。3.存活与死亡组比较,死亡组患者IL-2、IL-4、IL-6、IFN-γ、TNF-α水平高于存活组,差异有统计学意义（P<0.01）;死亡组患者IL-10水平低于存活组,差异有统计学意义（P<0.05）;两组患者的IFN-γ水平无明显差异。结论：动态检测ACLF患者的IL-2、IL-4、IL-5、IL-6、IL-10、IFN-γ、TNF-α水平,对病情轻重及转归有一定指导意义。 关键词：慢加急(亚急)性肝衰竭;细胞因子;临床意义     

Are 5-HT(1B/1D) and 5-HT(2A/2B/2C) receptors involved in learning and memory processes?

Pharmacological data provide clear evidence that 5-HT(1B/1D) and 5-HT(2A/2B/2C )receptors are involved in the consolidation of learning.     

A novel natural Nrf2 activator with PPARγ-agonist (monascin) attenuates the toxicity of methylglyoxal and hyperglycemia

Methylglyoxal (MG) is a toxic-glucose metabolite and a major precursor of advanced glycation endproducts (AGEs). MG has been reported to result in inflammation by activating receptor for AGEs (RAGE). We recently found that Monascus-fermented metabolite monascin acts as a novel natural peroxisome proliferator-activated receptor-γ (PPARγ) agonist that improves insulin sensitivity. We investigated the metabolic, biochemical, and molecular abnormalities characteristic of type 2 diabetes in MG-treated Wistar rats treated with oral administration of monascin or rosiglitazone. Monascin (a novel PPARγ agonist) activated nuclear factor-erythroid 2-related factor 2 (Nrf2) and down-regulated hyperinsulinmia in oral glucose tolerance test (OGTT). Monascin was able to elevate glyoxalase-1 expression via activation of hepatic Nrf2, hence, resulting in MG metabolism to d-lactic acid and protected from AGEs production in MG-treated rats. Rosiglitazone did not activate Nrf2 nor glyoxalase expression to lower serum and hepatic AGEs levels. Monascin acts as a novel natural Nrf2 activator with PPARγ-agonist activity were confirmed by Nrf2 and PPARγ reporter assays in Hep G2 cells. These findings suggest that monascin acts as an anti-diabetic and anti-oxidative stress agent to a greater degree than rosiglitazone and thus may have therapeutic potential for the prevention of diabetes.     

A new sulfonic acid derivative, (Z)-4-methylundeca-1,9-diene-6-sulfonic acid,isolated from the cold water sea urchin inhibits inflammatory responses through JNK/p38 MAPK and NF-κB inactivation in RAW 264.7

In this study, we isolated a new sulfonic acid derivative, (Z)-4-methylundeca-1,9-diene-6-sulfonic acid (1), from the sea urchin collected from the Sea of Okhotsk. We established the structure of this new compound by analysis of NMR and HRMS data, along with comparison of the data with those of the related compounds reported in the literature. In addition, we investigated its anti-inflammatory effects in LPS-stimulated RAW264.7 macrophages. Compound 1 inhibited the production of NO, iNOS, PGE₂, and COX-2, and it also suppressed the production of pro-inflammatory cytokines, such as TNF-α and IL-1β. It inhibited the translocation of the NF-κB subunit p65 into the nucleus by interrupting the phosphorylation and degradation of IκB-α. In addition, compound 1 significantly decreased the phosphorylation of JNK and p38 in LPS-stimulated RAW264.7 macrophages, suggesting that suppression of the inflammation process by compound 1 was mediated through the MAPK pathway. Taken together, this study showed that the anti-inflammatory effects of a new sulfonic acid derivative, (Z)-4-methylundeca-1,9-diene-6-sulfonic acid were mediated through the inhibition of NF-κB and JNK/p38 MAPK signaling pathways.     

Octocog alfa, antihaemophilic factor (recombinant), plasma/albumin free method (Advate®): a review of its use in the management of patients with haemophilia A

Octocog alfa, antihaemophilic factor, plasma/albumin free method (Advate?) is a recombinant, human, full-length coagulation factor VIII that does not contain human- or animal-derived plasma proteins. It is indicated for the control and prevention of bleeding episodes, for perioperative management and for routine prophylaxis in children and adults with haemophilia A. This article reviews the pharmacological properties, therapeutic efficacy and tolerability of Advate? in these patients. In previously treated paediatric and adult patients with moderately severe or severe haemophilia A, Advate? administered prophylactically, on demand or during surgery was effective for the prevention and treatment of bleeding episodes in three pivotal, uncontrolled clinical trials. The haemostatic efficacy of Advate? in these trials was rated as 'excellent' or 'good' in most bleeding episodes, with the majority of episodes being managed with one infusion. These findings were supported by pooled analyses of clinical trials and routine clinical practice studies, including the Post-Authorization Safety Study. Additionally, in a comparative study, routine prophylaxis with Advate? administered in a standard regimen or in a pharmacokinetic-tailored regimen was effective for the prevention of bleeding episodes in patients with moderately severe or severe haemophilia A, with no significant difference between the two regimens in terms of efficacy. Moreover, any routine prophylaxis with Advate? was found to be more effective in preventing bleeding episodes than on-demand therapy with Advate?. Advate? was generally well tolerated in clinical trials and postmarketing studies, with the most common treatment-emergent adverse events being pyrexia and headache. Serious adverse events with Advate? therapy are development of high-titre factor VIII inhibitors (usually in previously untreated patients) and hypersensitivity reactions. As expected, the incidence of factor VIII inhibitors (any titre) appeared to be lower in previously treated patients (≤ 1.8%) than in previously untreated patients (≤ 20%). There are no head-to-head comparative trials of Advate? and other factor VIII concentrates. Nevertheless, current evidence indicates that Advate? is an effective option for the management of paediatric and adult patients with haemophilia A.     

Selective inhibition by 4,α-dimethyl-m-tyramine (H77/77) and 4-methyl-α-ethyl-m-tyramine (H75/12) of the monoamine oxidase within serotonergic and noradrenergic neurons in the rat brain

Summary 1. The inhibition of monoamine oxidase (MAO) by 4,-dimethyl-m-tyramine (H77/77) and 4-methyl--ethyl-m-tyramine (H75/12), two amine releasing compounds, within monoaminergic neurons in the rat hypothalamus and striatum in vivo was determined. This was performed by measuring the protection of MAO by the test compound against the irreversible inhibition produced by phenelzine. The MAO activity inside and outside monoaminergic synaptosomes in homogenates of brain tissue was measured in the absence and presence of selective uptake inhibitors at low concentrations of ¹⁴C-labelled 5-hydroxytryptamine, noradrenaline or dopamine. 2. It was found that H77/77 and H75/12 produced a pronounced protection against phenelzine within the serotonergic and noradrenergic neurons, whereas much less effect was observed outside these neurons. 3. It was shown that the protection by H75/12 within the serotonergic neurons was somewhat reduced in 5-HT depleted reserpinized rats and that the protection outside these neurons was abolished. Some of the protection of MAO might therefore have been brought about by 5-HT molecules released by H75/12. 4. The marked inhibition of MAO within serotonergic and noradrenergic neurons was counteracted by amine uptake inhibitors and is accordingly brought about by the high concentrations of the accumulated compounds. 5. In contrast to other neuron selective MAO inhibitors, H75/12 decreased the 5-HT concentration in the hypothalamus showing that the releasing effect dominated over the MAO inhibitory effect. Send offprint requests to S. B. Ross at the above address