Pretreated Oenan the Javanica extract increases anti-inflammatory cytokines, attenuates gliosis, and protects hippocampal neurons following transient global cerebral ischemia in gerbils

Recently,we have reported that Oenanthe javanica extract(OJE)displays strong neuroprotective effect against ischemic damage after transient global cerebral ischemia.However,neuroprotective mechanisms of OJE have not been fully identified.Thus,this study investigated the neuroprotection of OJE in the hippocampal CA1 area and its anti-inflammatory activity in gerbils subjected to 5 minutes of transient global cerebral ischemia.We treated the animals by intragastrical injection of OJE(100 and 200 mg/kg)once daily for 1 week prior to transient global cerebral ischemia.Neuroprotection of OJE was observed by immunohistochemistry for neuronal nuclear antigen and histofluorescence staining for Fluoro-Jade B.Immunohistochemistry of glial fibrillary acidic protein and ionized calcium-binding adapter molecule 1 was done for astrocytosis and microgliosis,respectively.To investigate the neuroprotective mechanisms of OJE,we performed immunohistochemistry of tumor necrosis factor-alpha and interleukin-2 for pro-inflammatory function and interleukin-4 and interleukin-13 for anti-inflammatory function.When we treated the animals by intragastrical administration of 200 mg/kg of OJE,hippocampal CA1 pyramidal neurons were protected from transient global cerebral ischemia and cerebral ischemia-induced gliosis was inhibited in the ischemic hippocampal CA1 area.We also found that interleukin-4 and-13 immunoreactivities were significantly increased in pyramidal neurons of the ischemic CA1 area after OJE pretreatment,and the increased immunoreactivities were sustained in the CA1 pyramidal neurons after transient global cerebral ischemia.However,OJE pretreatment did not increase interleukin-2 and tumor necrosis factor-alpha immunoreactivities in the CA1 pyramidal neurons.Our findings suggest that pretreatment with OJE can protect neurons and attenuate gliosis from transient global cerebral ischemia via increasing expressions of interleukin-4 and-13.The experimental plan of this study was reviewed and approved by the Institutional Animal Care and Use Committee(IACUC)in Kangwon National University(approval No.KW-160802-1)on August 10,2016.

Pro-and anti-inflammatory cytokines profiles among Nigerian children infected with Plasmodium falciparum malaria

Objective:To examine array of some pro- and anti-inflammatory cytokines,namely, interleukin-4(IL-4),interleukin-10(IL-10),interferon-γ(IFN-γ),interleukin-5(IL-5), interleukin-6(IL-6),interleukin-12(IL-12) and tumor necrosis factor-α(TNF-α) concentrations in some Nigerians with falciparum malaria.Methods:Sera were obtained from the blood samples of 96 Nigerian children with Plasmodium falciparum infection.The sera were subjected to cytokine evaluation using commercial standard enzyme linked immunosorbent assay kits(Abcam,UK).Results:Mean pro-inflammatory cytokines in serum of children with uncomplicated and complicated malaria were IL-5 482.2 pg/mL versus 526.7 pg/mL,IL-6 98.8 pg/mL versus 82.6 pg/mL,IL-12 24.1 pg/mL versus 15.9 pg/mL,TNF-α107 pg/mL versus 511.7 pg/mL and IFN- 7 2.1 pg/mL versus 2.5 pg/mL.The anti-inflammatory cytokines status of IL-4 were 4.7 pg/mL versus 20.3 pg/mL,and IL-10 were 216 pg/mL versus 143.8 pg/mL in uncomplicated versus complicated/severe malaria cases.Participants with uncomplicated malaria had mean parasitaemia level of 3 158.9 parasites/μL while mean parasitaemia level for participants with complicated malaria was 12 550.5 parasite/μL and this difference was statistically significant(χ~2 =5 614.6,P【0.05).The difference between mean haemoglobin level for uncomplicated malaria(9.6 g/dL) and severe malaria(3.9 g/dL) was statistically significant (χ~2 = 2.3,P【0.05).The relationship between serum level of IL-6,IL-12,IFN-γ,IL-10 and IL-4 and ages showed positive correlation at r=0.92,0.99,0.86,0.95 and 0.85,respectively;while IL-5 and TNF-αhad negative correlation at r=-0.99 and -0.99,respectively.Conclusion: IL-4,IL-5,IL-6,IL-10,IL-12,TNF-αand IFN-γare involved in the immunopathology and immunoregulation of uncomplicated and complicated malaria infections.IL-6,IL-12,IFN-γand IL-10 depressed in complicated/severe malaria may not provide any protective immunity and may be indicators of poor prognosis in Plasmodium falciparum infected Nigerian children.

Relationship between pro-and anti-inflammatory cytokines profiles and some haematological parameters in some Cameroonians infected with Onchocerca volvulus

Objective:To investigate the relationship between white blood cells,lymphocytes,monocytes, and Interleukin(IL)-1α,IL-6.IL-10 and IL-13 production in Cameroonians with Onchocerca volvulus(O.volvulus) infection.Methods:A lolal of 357 individuals from five sites at Upper Sanga.Lekkie.Nyoug.Kelle and Sanaga Maritime divisions and located along Sanaga valley of Sanaga River in South Cameroon were screened for the presence of O.volvulus using the skin snip.The levels of the interleukins(IL-) namely IL-1α,IL-6,IL-10 and IL-13 were evaluated using enzyme linked immunoabsorbent assay techniques.Haematological parameters were evaluated using standard laboratory automated analyser.Results:O.volvulus microfilariae were found in skin tissues of 85(23.81%) volunteers.The mean interleukin(IL-) levels in the 0,volvulus control and infected individuals were IL-1αin(1.65±0.79 and 2.31±0.5) pg/ml.:IL-6 in(278.36±55.34 and 20l.74±34.56) pg/ml.:IL-10 in(436.03±208.64 and 418.49±I47.88) pg/ml.and IL-13 in(8.98±7.28 and 3S.06±11.92) pg/mL.There was a negative correlation between monocyte counts and IL-10 concentration in positive individuals.A negative correlation of IL-6 with while blood cell and lymphocyte counts was observed(P【0.05).The level of IL-13 was positively associated with microfilaria]load(P【0.05).Conclusions:We observed depressed IL-6 and raised IL-13 concentrations in the sera of individuals with onchocerciasis which implicate these interleukins in the immunological responses of the disease.Therefore,these IL-6 and IL-13 are associated with O.volvulus infection among Cameroonians.

Effects of structural modification of anti-inflammatory steroidal antedrug on pro-inflammatory mediators and inhibitory cytokines in human alveolar epithelial cells

The anti-inflammatory effects of the new ster-oidal antedrug, 21-acetyloxy-9α-fluoro-11β-hy-droxyl-3, 20-dioxo-1, 4-pregnadieno-[16α, 17α-d] isoxazoline (FP-ISO-21AC), on nitric oxide (NO) and interleukin 8 (IL-8) production, were inves-tigated together with its parent steroid predni-solone (PRED). PRED is one of the anti-in-flammatory steroids but has systemic side ef-fects which limit the use of it. PRED was modi-fied with ‘antedrug concept’ to create safer drugs that attack problems such as inflamma-tion, then quickly become inactive before they can cause systemic side effect. We had a test about the effect of the modified anti-inflamma-tory steroidal antedrug on anti-inflammatory activity. The present study evaluated their ability to inhibit cytokine-induced NO and IL-8 produc-tion in human alveolar epithelial cells. We also investigated their ability to enhance the expres-sion of inhibitory cytokine receptor, interleukin 22 receptor (IL-22R) in human alveolar epithelial cells. Our results showed that FP-ISO-21AC sh- owed higher ability to inhibit the cytokine - in-duced production of NO than PRED. Exogenous IL-22 was added to the media of both human alveolar epithelial cells (A549) and human lung fibroblast (HLF-1). In the presence of the ex-ogenous inhibitory cytokine IL-22, further re-duction of NO production was observed in A549 cells, which express IL-22R, but not in HLF1, which does not express IL-22R. These data suggested that the steroidal antedrugs en-hanced the expression of IL-22R. FP-ISO- 21AC showed higher potency than PRED to restore the expression of IL-22R. FP-ISO-21AC further reduced NO production to 27% and PRED further reduced NO production to 39%. In con-clusion, a synthesized steroidal antedrug FP- ISO-21AC showed higher anti-inflammatory ef-fects than PRED by inhibiting the expression of pro-inflammatory mediator NO and stimulating the expression of IL-22R.

Pharmacological evaluation of a novel enhydrazone ester (CEE-1) as a dual inhibitor of the release of pro-inflammatory cytokines and prostanoids from human monocytes

CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate)—a novel enhydrazone ester, was tested in vitro for anti-inflammatory activity against the release of pro-inflammatory cytokine and prostanoid from lipopolysaccharide-activated human monocytes or human monocytic cell line (U937). The effects were compared with those of standard anti-inflammatory drugs dexamethasone and indomethacin. CEE-1 potently and strongly inhibited the release of both tumor necrosis factor-alpha (TNF-α) and prostaglandin E2 (PGE2). The concentrations producing 50% inhibition (IC50 values) were 2.0 μM and 2.4 μM for TNF-α and PGE2, respectively. At 30 μM, the drug achieved almost complete inhibition of both mediators. Dexamethasone had similar effects but indomethacin inhibited only the PGE2 release, and although CEE-1 was less potent than these two drugs, it had comparable efficacy. The compound appeared to act, at least, in part by inhibiting the up-regulation of the mRNA for TNF-α as well as that of the prostanoid-synthetic enzyme, cyclo-oxygenase-2 (COX-2). However, like dexamethasone, but unlike indomethacin, CEE-1 did not affect COX-2 enzyme function. Thus, the profile of activity of CEE-1 is similar to that of steroids rather than the non-steroidal anti-inflammatory drugs. Structure-activity study showed that the presence of a simple aromatic ring attached via an NH-NH group was critical for activity. At the concentrations that completely inhibited mediator release, the compound displayed no significant in vitro toxicity on the cells. These results show that CEE-1 is a dual inhibitor of the release of cytokines and prostanoids, and therefore could be a potential alternative to steroids in the treatment of inflammatory diseases.

Role of inflammatory cytokines in peripheral nerve injury

Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.

阻断炎症因子转化生长因子-β改善细菌脓毒症T细胞增殖抑制的实验研究

目的:探究炎症细胞因子在脂多糖所致脓毒症免疫麻痹T细胞免疫抑制中的作用。方法:以革兰阴性细菌成分脂多糖诱导脓毒症T淋巴细胞免疫抑制,采用流式细胞分析检测对照组和模型组树突状细胞的促炎细胞因子白细胞介素(Interleukin,IL)-1、IL-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)-α和抗炎细胞因子IL-10、IL-17、转化生长因子(Transforming Growth Factor,TGF)-β的表达情况。结果:与对照组相比,模型组树突状细胞的促炎细胞因子IL-1、IL-6和TNF-α阳性率显著升高(P<0.05),抗炎细胞因子TGF-β阳性率显著升高(P<0.05),抗炎细胞因子IL-10、IL-17阳性率差异无统计学意义(P>0.05)。阻断TGF-β可逆转脂多糖诱导的脓毒症T淋巴细胞增殖抑制现象。与模型组相比,αTGF-β+模型组T细胞增殖反应显著升高(P<0.05)。结论:脂多糖所致脓毒症过程中树突状细胞促炎细胞因子IL-1、IL-6和TNF-α表达上调可能参与促炎反应过程。抗炎细胞因子TGF-β表达上调可能参与淋巴细胞凋亡的脓毒症免疫抑制过程。阻断TGF-β,改善细菌脂多糖诱导的免疫麻痹T细胞增殖抑制现象。

PLGA-姜黄素纳米颗粒的制备及体外抗炎性能评价

以聚乙烯醇(PVA)水溶液为水相,聚乳酸-羟基乙酸共聚物(PLGA)和姜黄素(Cur)的二氯甲烷溶液为油相,采用水包油包水的双乳液法制备了包载姜黄素的PLGA纳米颗粒(PLGA@Cur NPs),改善了姜黄素的分散性,提高了其抗氧化和抗炎性能.动态光散射粒度仪(DLS)和扫描电子显微镜(SEM)表征结果显示, PLGA@Cur3呈均匀的球形,平均尺寸为(340±15) nm,多分散指数(PDI)为(0.22±0.01),电位为(-20.2±4.2) mV,具有良好的稳定性.高效液相色谱(HPLC)分析结果表明,PLGA@Cur3 NPs中Cur的包封率为15.09%,载药率为34.85%.细胞水平结果显示, PLGA@Cur NPs具有良好的生物相容性,能够清除多种活性氧(ROS),有效降低RAW 264.7巨噬细胞分泌的促炎细胞因子含量,缓解细胞水平的炎症.

Hydrogen peroxide mediates pro-inflammatory cell-to-cell signaling: a new therapeutic target for inflammation?

Nitric oxide is now universally recognized as an extracellular signaling molecule. Nitric oxide, produced in one cell, diffuses across the extracellular space and acts with targets in an adjoining cell. In this study, we present proof that hydrogen peroxide - like nitric oxide - acts as a true first (intercellular) messenger for a multitude of pro-inflammatory ligands. RAW 264.7 macrophages were activated with three different ligands, lipopolysaccharide, interferon-gamma or advanced glycation end products in the presence of increasing concentrations of (hydrogen peroxide scavenging) catalase. As inflammatory readouts, nitric oxide and tumor necrosis factor were determined. We hypothesize that hydrogen peroxide travels between cells propagating the signal, then a certain percentage of the readout should be inhibited by catalase in a concentration- dependent manner. The experiment showed concentration-dependent inhib让ion of nitric oxide and tumor necrosis factor-a production in response to all three ligands/ligand combinations (interferon-gamma, lipopolysaccharide, and chicken egg albumin-derived advanced glycation end product) in the presence of increasing concentration of catalase. For example, catalase inhibited 100% of nitric oxide and 40% of tumor necrosis factor-a production at its highest concentration. Our results suggest that hydrogen peroxide travels through cell membranes into the extracellular space and enters and activates ad;acent cells. Like rdtric oxide, we suggest that it is a ubiquitous first messenger, able to transmit cell-to-cell pro-inflammatory signals such as nitric oxide and tumor necrosis factor-a. In a therapeutic setting, our data suggest that compounds acting as hydrogen peroxide scavengers might not even need to enter the cell to act as anti-inflammatory drugs.

Differences in the Histopathology and Cytokine Expression Pattern between Chronological Aging and Photoaging of Hairless Mice Skin

Skin photoaging is a complex, multifactorial process resulting in functional and structural changes of the skin, and different phenotypes from chronological skin aging are well-recognized. Ultraviolet (UV)-irradiated hairless mice have been used as a skin photoaging animal model. However, differences in morphology and gene expression patterns between UV-induced and chronological skin changes in this mouse model have not been fully elucidated. Here we investigated differences in histopathology and cytokine expression between UV-irradiated and non-irradiated aged hairless mice to clarify the factor(s) that differentiate photoaging from chronological skin aging phenotypes. Eight-week-old HR-1 hairless mice were divided into UV-irradiated (UV-irradiated mice) and non-irradiated (control mice) groups. Irradiation was performed three times per week for 10 weeks. In addition, 30-week-old HR-1 hairless mice were reared until 70 weeks of age without UV irradiation (aged mice). Histopathologies revealed that the flattening of dermal-epidermal junctions and epidermal thickening were observed only in UV-irradiated mice. Decreases in fine elastic fibers just beneath the epidermis, the thickening of elastic fibers in the reticular dermis, and the accumulation of glycosaminoglycans were more prominent in UV-irradiated mice as compared to non-irradiated aged mice. Quantitative PCR analyses revealed that UV-irradiated mice showed an increase in the expression of IFN-γ. In contrast, aged mice exhibited proportional up-regulation of both pro-inflammatory and anti-inflammatory cytokines. The IFN-γ/IL-4 ratio, an indicator for the balance of pro-inflammatory and anti-inflammatory cytokines, was significantly higher in UV-irradiated mice as compared to control and non-irradiated aged mice. An elevated IFN-γ/IL-4 ratio was also observed in aged senescence-accelerated mouse-prone 1 (SAMP1) mice, a spontaneous skin photoaging model we recently reported. Thus, an imbalance between pro-inflammatory and anti-inflammatory cytokines might be a key factor to differentiate photoaged skin from chronologically-aged skin.

1,3-二环己基-1,2,3,6-四氢嘧啶-4,5-二甲酸二乙酯的抗炎镇痛作用

目的探讨1,3-二环己基-1,2,3,6-四氢嘧啶-4,5-二甲酸二乙酯(ZL-5010)体内、体外的抗炎镇痛活性。方法醋酸所致小鼠扭体反应模型评价镇痛作用;二甲苯致小鼠耳廓肿胀模型和角叉菜胶致大鼠足跖肿胀模型评价抗炎作用。细菌脂多糖(LPS,10μg/mL)刺激小鼠腹腔渗出细胞活化作为体外炎症模型。ELISA法检测白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的含量。结果 ZL-5010经灌胃给药,1次/d,连续3 d,在0.25和0.5 0 mmol/kg的剂量下能减少醋酸所致小鼠的扭体次数,抑制二甲苯所致的小鼠耳廓肿胀,抑制角叉菜胶诱导的大鼠足跖肿胀,均具有统计学意义(P<0.05);ZL-5010体外能抑制LPS诱导的小鼠腹腔渗出细胞产生促炎细胞因子IL-1β和TNF-α,具有统计学意义的最低有效浓度分别为10和20μmol/L(P<0.05)。结论首次发现ZL-5010经动物体内灌胃给药具有抗炎镇痛作用,体外可抑制小鼠腹腔渗出细胞产生促炎细胞因子IL-1β和TNF-α。

花艽-6抗炎作用及其机理研究

本试验旨在研究和探讨抗类风湿性关节炎(rheumatoid arthritis,RA)药物花艽-6的抗炎作用及其抗炎机理。采用二甲苯致小鼠耳肿胀法、醋酸致小鼠毛细血管通透性增高法、甲醛和蛋清致小鼠足跖肿胀法,以及棉球致小鼠肉芽组织增生法分别研究了该药物的抗急性、亚急性和慢性炎症的作用。通过复制佐剂性关节炎(adjuvant arthritis,AA)大鼠模型研究花艽-6对其血清中IL-1βI、L-6和TNF-α含量的影响。花艽-6对小鼠二甲苯所致的耳肿胀、醋酸所致的腹腔毛细血管通透性增高、甲醛和蛋清所致的足跖肿胀和棉花所致的肉芽组织增生均具有显著或极显著的抑制作用。花艽-6具有抗炎作用,可显著降低AA大鼠血清中IL-1βI、L-6和TNF-α的表达,对RA具有治疗作用。

黄连解毒汤对2型糖尿病大鼠细胞因子IL-4和IL-10水平的影响

目的:探讨黄连解毒汤对2型糖尿病大鼠血清抗炎细胞因子水平的影响,分析其改善胰岛素抵抗的作用机理。方法:观察黄连解毒汤对实验性2型糖尿病大鼠治疗前后血糖(FBG)、胰岛素(FINS)、血清白介素-4(IL-4)和白介素-10(IL-10)等指标的影响。结果:给予黄连解毒汤治疗的实验性2型糖尿病大鼠,其血清FBG水平显著低于模型组(P<0.01),FINS和模型组比较无显著差异;IL-4和IL-10水平明显高于模型组(均P<0.01)。结论:黄连解毒汤及其主要有效成分小檗碱具有提高2型糖尿病大鼠血清抗炎细胞因子IL-4和IL-10水平的作用,改善其慢性炎性反应和胰岛素抵抗。

高效表达重组猪IL-10的基因工程菌株的构建

白细胞介素 10(IL 10)是一种Th2细胞等产生的能抑制Th1细胞释放细胞因子的免疫调节因子。从经脂多糖(LPS)活化的猪外周血单核细胞(PBMC)中提取总RNA,用RT PCR扩增了猪IL 10(poIL 10)编码基因,克隆并测序验证后,将其亚克隆到表达载体pPROEXTMHTb中,转化DH5α后,用IPTG诱导培养,经免疫印迹和生物活性检测显示,重组菌株表达了具有活性的重组poIL 10,重组poIL 10表达水平达3mg/ml培养液,占菌体细胞总蛋白的30 2%,本研究为poIL 10的功能研究和临床应用奠定了基础。

5-氟尿嘧啶对大鼠急性胰腺炎炎症相关细胞因子的调节作用

目的 观察 5 -氟尿嘧啶 (5 FU )对急性胰腺炎 (AP )时的致炎细胞因子和抗炎细胞因子的调节作用 ,探讨 5 FU治疗AP的作用机理。方法 将健康雄性SD大鼠随机分成假手术组 (n =6)和AP模型组 (n =2 4)及 5 FU治疗组 (n =2 4)。其中 ,AP模型组和 5 FU治疗组分别再分为成模后或治疗后 2 ,6和 2 4h 3个观察亚组。分别抽取假手术组、AP组各亚组和 5 FU组各亚组大鼠静脉血 ,检测TNF α ,IL 1,IL 6,IL 10和TGF β的水平。检测假手术组、AP组 2 4h亚组和 5 FU组2 4h亚组大鼠血淀粉酶和白细胞。抽血后处死各组大鼠 ,称胰腺湿重。结果 AP组大鼠血中致炎细胞因子 (TNF α ,IL 1,IL 6)和抗炎细胞因子 (IL 10 ,TGF β)均显著增高 ;5 FU治疗后 ,所有检测细胞因子均下降 ,其中TNF α ,IL 1,IL 6在 2 ,6h亚组下降明显 (P <0 .0 5 ) ,IL 10和TGF β在治疗后 6,2 4h亚组下降明显 (P <0 .0 5 )。假手术组 ,AP组 2 4h亚组和 5 FU组 2 4h亚组大鼠胰腺湿重分别为 (0 .5 3± 0 .0 9) g ,(1.5 3± 0 .13 ) g和 (0 .88± 0 .13 )g ;血淀粉酶分别为 (3 74.2± 92 .84)U /L ,(1817.2 5± 45 9.3 5 )U /L和 (797.4± 2 2 5 .9)U /L。 5 FU治疗后 ,胰腺湿重和血淀粉酶均较AP组明显下降 (均P <0 .0 5 )。结论 5 FU可同时抑?

食品-家兔体温-免疫调节的因果关系研究

通过用滋补类食品山药和清热类食品苦瓜、苦荞麦和酸奶饲喂家兔,研究其体温和主要抗炎与发炎细胞因子的变化规律,分析食品与细胞因子网络和体温的因果关系,揭示食品对机体的免疫调节作用。结果表明:对喂食山药后的家兔24h的跟踪结果为体温升高;细胞因子浓度降低的有:IL-1ra、IL-4、TGF-β、TNF-α、INF-γ、IL-12。升高的有:IL-6、IL-10、IL-1β。对喂食酸奶后家兔24h的跟踪结果为体温降低;细胞因子浓度降低的有:IL-1ra、IL-4、TGF-β、IL-1β、TNF-α、INF-γ;升高的有:IL-6、IL-10、IL-12。喂食苦瓜后家兔对24h跟踪结果为体温降低;细胞因子浓度降低的有:IL-1ra、TGF-β、IL-1β、TNF-α、INF-γ,升高的有:IL-4、IL-6、IL-10、IL-12。对喂食苦荞麦后家兔24h跟踪结果为体温降低;细胞因子浓度降低的有:IL-1ra、IL-4、TGF-β、IL-1β、TNF-α、INF-γ,升高的有:IL-6、IL-10、IL-12。说明食品可以通过肠黏膜信号途径调节细胞因子网络,从而调节免疫细胞网络和活性。但其作用规律非常复杂,往往既可以刺激发炎细胞因子的升高(或降低),也可以刺激抗炎细胞因子的升高(或降低)。不同食品对体温的作用则比较有规律,其中滋补类食品使动物的体温升高,而清热类食品则可以刺激动物体温降低,其变化都在正常体温范围内。实验证明饲喂不同的食品可以调节细胞因子网络,从而调节机体的免疫网络,进而表现出体温的变化。它们存在一定的因果关系。

炎症相关细胞因子表达升高与类风湿关节炎病情程度的相关性分析

目的检测类风湿关节炎(RA)患者血清中细胞因子的含量,探讨炎性相关细胞因子联合检测对RA病情程度评估的临床应用价值。方法募集RA患者28例和同期15例健康体检者。多重微球流式免疫荧光发光法检测白细胞介素1β(IL-1β)、IL-2、IL-5、IL-6、IL-8、IL-12P70、IL-17、肿瘤坏死因子α(TNF-α)、α干扰素(IFN-α)、IFN-γ、IL-4、IL-10炎症相关细胞因子表达情况,全自动生化分析仪检测C反应蛋白(CRP),魏氏法测量红细胞沉降率(ESR),获取炎症指标数据。计算RA组患者28关节疾病活动指数(DAS28),比较各细胞因子与RA疾病活动度的曲线下面积,分析RA患者炎症相关细胞因子血清水平与CRP、ESR的相关性。结果RA患者血清中IL-2、IL-6、IL-12P70、IL-4、IL-10与RA疾病活动度的指标DAS28-CRP显著相关,IL-12P70、TNF-α、IL-4与RA疾病活动度的指标DAS28-ESR显著相关,反映RA患者病情程度的指标CRP与IL-6(r=0.515)、IL-12P70(r=0.530)、IL-4(r=0.539)、IL-10(r=0.434)呈正相关,ESR与IL-6(r=0.403)、IL-12P70(r=0.475)、TNF-α(r=0.497)、IL-4(r=0.450)呈正相关。与CRP、ESR正常组比较,CRP异常组中IL-6、IL-12P70、IL-2、IL-4、IL-10水平升高,ESR异常组中IL-12P70、IL-4、TNF-α水平升高。RA组患者IL-8、IFN-α、IFN-γ表达较健康组升高。结论血清中炎症相关细胞因子检测对RA的早期诊断和病情程度判断有重要的参考价值,可作为确诊RA的重要预测指标。

抑炎因子IL-35与移植肾功能延迟恢复关系的研究

目的探讨白细胞介素(IL)-35与移植肾功能恢复情况之间的关系。方法回顾性分析45例心脏死亡器官捐献(DCD)供肾肾移植受体的临床资料。根据肾移植术后是否发生移植物功能延迟恢复(DGF),所有受体分为早期肾功能恢复良好(IGF)组(32例)和DGF组(13例)。比较肾移植术后1、2、3、7、14、28 d及术后3个月、6个月、1年各时间点两组受体的血清肌酐(Scr)和估算肾小球滤过率(e GFR)水平;比较肾移植术后1、2、3、7、14、28 d各时间点两组受体血清和尿液IL-35含量。结果 DGF组受体术后肾功能恢复迟缓,术后7 d时Scr水平高于IGF组,e GFR水平低于IGF组,差异均有统计学意义(均为P<0.05)。术后1年,两组受体Scr水平的差异无统计学意义,但e GFR仍存在较大差异,与IGF组相比,DGF组受体术后1年时e GFR仍降低(P<0.05)。术后1、2、3、7、14 d,DGF组血清中IL-35含量均低于IGF组,两组比较差异均有统计学意义(均为P<0.05);术后28 d,与IGF组相比,DGF组血清IL-35含量反而升高,两组比较差异有统计学意义(P<0.05)。术后1、2、3、7 d,DGF组尿液中IL-35含量均低于IGF组,两组比较差异均有统计学意义(均为P<0.05);术后14、28 d,两组受体尿液IL-35含量进行比较,差异均无统计学意义(均为P>0.05)。结论肾移植术后受体血清和尿液中IL-35含量低与DGF发生存在一定的联系,提示术后早期受体全身和移植肾局部抑炎应答过弱,过度的炎症应答得不到有效控制,可能是DGF发生的重要原因。

加兰他敏对心肌缺血再灌注损伤大鼠血清CK-MB活性及TNF-α和IL-6水平的影响

目的:探讨加兰他敏对心肌缺血再灌注损伤(MIRI)大鼠血清肌酸激酶(CK-MB)活性和肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平的影响。方法:SPF级雄性SD大鼠50只,随机均分为假手术组、心肌缺血再灌注(I/R)组、加兰他敏组、联合A组及联合B组;在5组大鼠左冠状动脉前降支(LAD)下穿线,假手术组穿线不结扎,其余4组大鼠穿线后结扎LAD 30 min后,再松开结扎线再灌注120 min,制作I/R模型,假手术组及I/R组造模前30 min静脉注射生理盐水(2 m L/kg),其余3组注射加兰他敏(4 mg/kg),联合A组在造模前45 min还注射阿托品(4 mg/kg)、联合B组在造模前45 min还切断两侧迷走神经;5组大鼠再灌注120 min后,测定大鼠血清CK-MB活性及TNF-α、IL-6水平,取心肌组织进行HE染色,光镜下观察心肌结构。结果:与假手术组比较,I/R组CK-MB活性、TNF-α及IL-6水平升高(P<0.05),提示造模成功;与I/R组比较,加兰他敏组CK-MB活性、TNF-α和IL-6水平降低(P<0.05);与加兰他敏组比较,联合A组及联合B组CK-MB活性、TNF-α和IL-6水平升高(P<0.05);400×光镜视野下见假手术组心肌纤维排列整齐,I/R组心肌结构紊乱,可见细胞坏死和炎性细胞浸润,加兰他敏组心肌纤维排列较整齐,仅见水肿和少许炎性浸润,联合A组及联合B组心肌细胞排列紊乱,心肌水肿,组织间隙有炎性细胞浸润。结论:加兰他敏可能通过胆碱能抗炎通路减少炎性因子的产生,从而减轻心肌MIRI。

β_2GPI/抗β_2GPI抗体复合物激活THP-1细胞内TRIF途径

目的:观察β2GPI/抗β2GPI抗体复合物能否激活单核细胞株THP-1的TRIF途径,以探讨TRIF依赖途径在抗磷脂综合征(APS)发病机制中的作用。方法:采用一定剂量β2GPI/抗β2GPI抗体复合物刺激THP-1细胞一定时间,收集细胞总RNA及总蛋白,荧光定量PCR(RT-PCR)检测细胞TRIF mRNA水平,Western blot检测细胞TRIF蛋白表达情况;进一步观察TLR4途径抑制剂-TAK-242是否干预β2GPI/抗β2GPI抗体复合物对TRIF的诱导表达以及相关细胞因子IL-6、IL-8、TNF-α的表达。结果:β2GPI/抗β2GPI抗体复合物(100 mg/L)能够诱导THP-1细胞表达TRIF(mRNA及蛋白),并显示时间效应,分别于刺激1 h和2 h时TRIF mRNA及蛋白表达至高峰。TAK-242(5μmol/L)能够明显抑制β2GPI/抗β2GPI抗体复合物对THP-1细胞TRIF的诱导表达,同时抑制IL-6、IL-8、TNF-α等炎症因子的表达。结论:TRIF依赖的TLR4途径参与了β2GPI/抗β2GPI抗体复合物对THP-1细胞的激活,提示其在抗磷脂综合征的病理机制中发挥一定作用。