促炎和抗炎细胞因子在重症胰腺炎发病机制中的作用

目的 探讨促炎和抗炎细胞因子及其平衡与重症胰腺炎（ＳＡＰ）的关系。方法 ２６例ＳＡＰ病人分为血液滤过组和对照组。测定血清内促炎细胞因子ＴＮＦα、ＩＬ－１β、ＩＬ－８、ｓＩＬ－２Ｒ及抗炎细胞因子ＩＬ－２、ＩＬ－１０的含量，观测ＡＰＡＣＨＥⅡ评分、ＣＴ积分和体液细菌培养及临床症状的变化，以观察促炎和抗炎细胞因子与疾病严重度、胰腺坏死、机体免疫力及腹痛的关系。结果 ＡＰＡＣＨＥⅡ及ＣＴ积分显著降低和腹痛（Ｐ〈０．０５）时间显著缩短；体液细菌培养时间显著延迟和阳性率降低（Ｐ〈０．００５）。血滤组的促炎细胞因子较对照组显著降低，而抗炎细胞因子却显著升高（Ｐ〈０．０５）。结论 促炎和抗炎细胞因子与重症胰腺炎的病理生理变化密切相关，且两者的相对变化较两者的绝对变化更为重要。     

连续性静脉-静脉血液滤过对内毒素休克羊血液动力学和炎性介质的影响

目的观察连续性静脉.静脉血液滤过(CVVH)对内毒素休克血液动力学和炎性介质的影响。方法 雄性绵羊12只,随机分为两组。对照组(A组,n=6),内毒素以1 mg·kg-1静脉泵注,30min内完成,同时静脉输注林格液15 ml·kg-1·h-1,持续6 h;血滤组(B组,n=6),于开始泵注内毒素后1 h给予CVVH治疗5 h,其余处理同A组。所有动物均给予气管插管、镇静、肌松、控制呼吸,行有创血液动力学监测;两组分别于内毒素泵注前(T0)、开始泵注后30、60、90、120、210、360 min(T1～T6)采静脉血及超滤液4ml,测定血浆及超滤液中内毒素、TNF-α、IL-6、IL-10的浓度。结果 血滤组CVVH治疗后(T1-T6)平均动脉压及体循环阻力指数明显上升、心率显著性下降。TNF-α于泵注内毒素后(T1-T6)两组均显著性增高,血滤组于CVVH治疗60 min(T4)时较治疗前(T2)虽无明显改变,但明显低于同时点对照组(P<0.01),CVVH治疗150～300 min(T5-T6)时TNF-α浓度较对照组及治疗前(T2)均显著性降低(P<0.05);IL-10虽呈增高趋势,但较治疗前和对照组无显著性变化;而两组IL-6水平则无明显差异。超滤液中可检测到TNF-α、IL-6、IL-10。结论 血滤治疗有利于纠正促炎细胞因子过度释放和抗炎细胞因子失衡,改善内毒素休克血液动力学。     

急性胰腺炎与细胞因子的研究进展

急性胰腺炎时胰腺组织释放细胞因子入血循环,使胰腺和血中细胞因子含量增加。这些细胞因子通过激活胰腺及远隔器官的细胞因子受体而发挥生物学效应,或导致胰腺及远隔器官损伤,介导致炎作用;或抑制促炎细胞因子释放,发挥抗炎作用。抑制促炎细胞因子基因表达,拮抗其生物学效应或转染抗炎细胞因子基因,增加其表达已成为临床治疗急性胰腺炎新思路。     

短时血滤对重症急性胰腺炎治疗的影响

探讨短时血滤对重症急性胰腺炎的疗效及机理。方法２０例患者随机分为血滤组和非血滤组,每组１０例。比较两组局部和全身表现,观察各时相点血液促炎细胞因子ＴＮＦα、ＩＬ－β、ＩＬ－６、ＩＬ－８和ｓＩＬ－２Ｒ和抗炎细胞因子ＩＬ－２和ＩＬ－１０含量。     

急性胰腺炎与细胞因子的研究进展

急性胰腺炎时胰腺组织释放细胞因子入血循环，使胰腺和血中细胞因子含量增加。这些细胞因子通过激活胰腺及远隔器官的细胞因子受体而发挥生物学效应，或导致胰腺及远隔器官损伤，介导致炎作用；或抑制促炎细胞因子释放，发挥抗炎作用。抑制促炎细胞因子基因表达，拮抗其生物学效应或转染抗炎细胞因子基因，增加其表达已成为临床治疗急性胰腺炎新思路。     

早期血滤对重症急性胰腺炎家猪血浆细胞因子水平的影响

目的　探讨早期血液滤过对重症急性胰腺炎 (SAP)家猪促抗炎细胞因子血浆水平的影响。方法　采用胰管逆行灌注人工胆汁的方法复制家猪SAP模型 ,随机分为胰腺炎血滤治疗组(HF组 ,n =8)和胰腺炎非血滤治疗组 (NHF组 ,n =8)。HF组使用高容量、零平衡血滤。用酶联免疫吸附试验检测两组动物建模前后血浆肿瘤坏死因子 (TNF) α、白细胞介素 (IL) 1β、IL 10的水平。结果　与NHF组相比 ,血滤治疗后HF组家猪TNF α、IL 1β的血浆水平较低 [血滤停止前( 618± 2 76)ng/L较 ( 13 75± 3 3 4)ng/L ;( 4 45± 14 1)ng/L较 ( 965± 2 65 )ng/L ,P <0 .0 1] ,IL 10与TNF α的比值较高 [血滤停止前 ( 0 .3 5 4± 0 .114 )较 ( 0 .12 5± 0 .0 3 2 ) ,P <0 .0 1]。结论　早期血滤能降低SAP家猪促炎细胞因子TNF α,IL 1β的血浆水平 ,升高IL 10 /TNF α的比值 ,使促抗炎细胞因子失衡得到部分纠正。     

血液透滤清除血清IL-6在重症急性胰腺炎治疗中的应用研究

目的探讨血液透滤清除IL-6在重症急性胰腺炎治疗中的作用及机理。方法根据诊断标准对2002年7月至2006年6月来我院就诊的178例重症急性胰腺炎患者随机分组：血滤组（HF组）85人,非血滤组（NHF组）93人。比较两组患者局部和全身表现,观察各时相点促炎细胞因子血清IL-6的测定值的差异。结果HF组与NHF组比较：腹痛腹胀持续时间为（18.8±4.2）hvs（89.7±28.1）h（P〈0.05）;治疗后第10天APACHEⅡ积分为（5.5±3.6）分vs（13.8±3.8）分（P〈0.05）;住院天数和医疗费为（28.2±12.4）天vs（42.4±11.2）天和（4.38±2.8）万元vs（7.46±2.2）万元,（P〈0.05）。治疗后各时相点血清IL-6检测结果：HF组较NHF组显著降低（P〈0.05）;MODS发病率和病死率分别为12.47%vs.36.28%和4.28%vs.12.82%,两者差异有统计学显著意义（P〈0.05）。结论早期短时血滤有利于纠正重症急性胰腺炎患者血清促炎细胞因子过度释放,使病情减轻,降低MODS发病率和病死率,提高疗效。     

早期血滤对家猪重症急性胰腺炎血浆细胞因子和脏器功能的影响

目的:观察早期血液滤过对重症急性胰腺炎(SAP)家猪血浆细胞因子水平和脏器功能的影响。方法:采用胰管逆行灌注人工胆汁法复制家猪SAP模型;随机分为胰腺炎血滤治疗组(HF组,n=8)和胰腺炎非血滤治疗组(NHF组,n=8)。HF组在建模成功后行高容量、零平衡血滤治疗。结果:与NHF组相比,HF组的MAP、CVP及PaO2/FiO2值均较高(P<0.01);心率、尿蛋白含量、血清ALT水平、肺系数与肺湿/干比均较低(P<0.05)。光镜下,HF组肺组织学评分较低(P<0.01);肾、肝组织损伤亦较轻。但胰腺组织学评分在两组间无差异。建模后6h,HF组血浆TNF鄄α、IL鄄1β水平较低(P<0.05);IL鄄10/TNF鄄α比值较高(P<0.05)。结论:早期血滤能有效地廓清SAP猪血浆中的细胞因子TNF鄄α和IL鄄1β,升高IL鄄10/TNF鄄α比值,改善血流动力学,并减轻肺、肾、肝组织损伤。     

实验研究细胞因子在急性胰腺炎发病机理中的作用

目的：观察大鼠血清中细胞因子在急性胰腺炎发病机理中的作用。方法：检测血清中细胞因子和TNF-α，观察胰、肝、肺、肾的病理变化及胰腺细胞培养液中淀粉酶和PLA_2化。结果：在坏死性胰腺炎和水肿性胰腺炎大鼠血清中，IL-1β、IL-6、IL-2和TNF-α都明显高于正常对照组(P＜0.01），水肿性和坏死性胰腺炎的胰组织中4种细胞因子都高于正常胰腺组（P＜0.01），但两者之间未见明显差别。水肿性胰腺炎分离培养的胰腺细胞上清液中测出IL-6和TNF-α都高于正常胰腺组。结论:急性胰腺炎症过程中有多种细胞因子参与发病机理，其在体内放大作用造成胰腺本身在内的全身多器官功能损害，而且细胞因子的升高与疾病的严重程度相关。     

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     

围术期麻醉对细胞因子的影响

麻醉可以直接或间接的影响机体免疫力一不同麻醉方式和不同麻醉药物对细胞因子产生不同影响。基于不同实验关手麻醉对免疫的影响有不同的结果,还需要进一步的研究。临床工作中选择适当的麻醉药物可以减轻术中及术后炎症反应,保护免疫功能。减少PMN凋亡,促进患者康复。     

The possible use of spleen cells for the adoptive immunotherapy of cancer patients

The possible use of spleen-derived mononuclear cells (SPMC) for the intentional and economical adoptive immunotherapy of cancer patients was studied. SPMC were obtained from spleens resected surgically from patients with gastric cancer or idiopathic thrombocytopenic purpura (ITP). When SPMC were cultured in recombinant interleukin 2 (rIL2), SPMC, in the form of interleukin-activated killer spleen cells (IL-SP) proliferated in six of eight cases. CD8+ lymphocytes were the major expanding cell population in most SPMC cultures and IL-SP showed a significant cytolytic activity against cultured tumor cells during cell proliferation. When cultured with a streptococcal preparation, OK-432, for 24 to 48 h, SPMC showed cytotoxic activity against tumor cells and were expressed as OK-432 activated killer spleen cells (OK-SP). The effects of supernatants from IL-SP and OK-SP on tumor cell growth were also examined. The supernatants from IL-SP and OK-SP significantly inhibited cell growth in 3 and 10 out of 11 cases, respectively, while those from OK-SP showed higher growth inhibitory activity than those from IL-SP. The results of this study indicate the potential of SPMC as effector cells for the adoptive immunotherapy of cancer patients.     

Renal allograft rejection: the temporal relationship and predictive value of plasma TNF (alpha and beta), IFN-gamma and soluble ICAM-1

Recently, close interactions have been described between the tumour necrosis factors alpha and beta (TNF-alpha and beta), interferon-gamma (INF-gamma) and intercellular adhesion molecule-1 (ICAM-1) in T-cell mediated immune activation. During the process of renal graft rejection, the properties of these cytokines to act as powerful stimulators of macrophages, to upregulate class II MHC expression and to stabilise cell-to-cell binding make them of great potential interest. The aim of the present study was to determine the plasma levels of each cytokine and soluble ICAM-1 in 16 renal allograft recipients. We examined plasmas of patients for the first 2 weeks after transplantation and correlated results with the clinical pattern of rejection. Our data suggest an immunopathologic involvement of TNF-alpha, TNF-beta and slCAM-1 in renal allograft rejection and showed that there was a significant elevation in plasma concentrations of these parameters 2 or 3 days prior to the diagnosis of clinical rejection. Rises in INF-gamma did not appear to be significant with regard to rejection as very high levels were found in patients showing no evidence of clinical rejection.     

仙茅苷对成骨细胞增殖分化和炎症因子表达的影响及机制分析

目的仙茅苷(curculigoside,CCG)能有效防治去卵巢大鼠的骨量丢失,但是其分子机制尚不清楚,因此,研究CCG在地塞米松(dexamethasone,DEX)诱导下对成骨细胞增殖分化和炎症因子释放的影响,并探讨其相关机制。方法将大鼠颅骨成骨细胞与DEX共同孵育24～72 h,同时采用不同浓度的CCG对其干预,采用细胞计数试剂盒检测成骨细胞增殖情况,流式细胞术检测成骨细胞线粒体膜电位(mitochondria membrane potential,MMP)和活性氧(reactive oxygen species,ROS)水平。酶联免疫吸附法检测肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-6、环氧合酶-2(cyclooxygenase-2,COX-2)、重组人胰岛素样生长因子-1(insulin-like growth factor-1,IGF-1)和巨噬细胞集落刺激因子(macrophage colony stimulating factor,M-CSF)等细胞因子的表达。采用蛋白质印迹法检测骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)、β-连环蛋白(β-catenin)、骨保护素(osteoprotegerin,OPG)、核因子κB受体活化因子配体(receptor activators of NF-κB ligand,RANKL)和核因子κB受体活化因子(receptor activator of NF-κB,RANK)的蛋白表达。结果地塞米松1μmol/L处理成骨细胞后,成骨细胞增殖明显低于未处理组,25～100μg/mL CCG预处理可明显逆转DEX对成骨细胞的杀伤作用。25～100μg/mL的CCG预处理可提高DEX诱导下成骨细胞的MMP水平,降低ROS的生成。此外,CCG明显逆转DEX对碱性磷酸酶(alkaline phosphatase,ALP)、OPG、BMP-2、β-catenin、IGF-1和M-CSF水平的抑制作用以及对RANKL和RANK等分化指标的促进作用。CCG还能抑制DEX诱导的TNF-α、IL-1β、IL-6、COX-2等炎症细胞因子的释放。结论这些结果为进一步研究CCG的成骨细胞保护机制提供了新的思路,通过诱导细胞增殖和分化,减少炎症反应,提示CCG可用于防治骨质疏松症。     

IMMUNE RESPONSE IN PATIENTS WITH PERSISTENT CANDIDURIA AND OCCULT CANDIDEMIA

PURPOSE: We evaluated the immunological response in patients with persistent candiduria with or without occult candidemia. MATERIALS AND METHODS: Levels of Thl (pro-inflammatory interleukin [IL]-1, IL-2 and tumor necrosis factor-alpha) and Th2 (anti-inflammatory IL-4 and IL-10) cytokines were measured in the sera of patients with persistent candiduria. Polymerase chain reaction assessment of the 158 base pair candidal actin gene was used to detect Candida albicans in blood to identify occult candidemia. RESULTS: During a 14-month period 66 hospitalized patients with a mean age of 63 years (range 44 to 80) with persistent candiduria were evaluated. Occult candidemia developed in 27 patients (41%) as evidenced by detection of candidal actin gene in the sera by polymerase chain reaction. Risk factors included antibiotics in 27 patients (100%), central venous catheter in 22 (81%), urinary catheter in 21 (78%), total parenteral nutrition in 18 (66%), diabetes mellitus in 16 (59%) and abdominal surgery in 14 (52%). A total of 17 age matched patients with a mean age of 59 years hospitalized for elective general or vascular surgical procedures with no clinical or laboratory evidence of urinary or hematogenous fungal or bacterial infection served as controls. Serum levels of Th2 cytokines were elevated in 18 of 39 patients with persistent candiduria alone, and in 22 of 27 patients with candiduria and occult candidemia compared to controls (p<0.002). Th1 cytokines were within normal limits or slightly decreased in all patients with persistent candiduria with or without candidemia. CONCLUSIONS: These observations indicate that an abnormal immune response develops in patients with persistent candiduria with or without candidemia.     

利奈唑胺对严重烧伤家兔炎症因子水平的影响

目的：研究利奈唑胺（LZD）对严重烧伤家兔促炎症因子肿瘤坏死因子-α（TNFα）、白介素-1β（IL-1β）、白介素-6（IL-6）水平的影响。方法：随机将24只家兔分为假烫组、烫伤组、假烫＋LZD治疗组、烫伤＋LZD治疗组4组,每组6只。将两烫伤组家兔背部皮肤置于98℃热水18s制备30％TBSAI III度烫伤模型;假烫组用37℃温水代替热水。两LZD治疗组家兔静脉注射10mg／kg利奈唑胺。组织病理学观察烫伤深度,采用放射免疫分析方法检测烧伤后家兔血清TNF—α、IL-1、β、IL-6水平。结果：与假烫组家兔比较,烧伤家兔TNF-α、IL-1β及IL-6显著升高,IL-1β在伤后12h达峰值,TNF-α及IL-6在伤后24h达峰值。利奈唑胺能显著降低烫伤家兔TNF-α、IL-1β及IL-6水平（P〈0．05）,降幅分别为28．19％、38．54％和28．48％,但利奈唑胺对假烫家兔3种细胞因子的水平无显著影响（P〉0．05）。结论：利奈唑胺能显著降低烫伤家兔的促炎症因子水平。     

Interleukin-8 expression is increased in senescent prostatic epithelial cells and promotes the development of benign prostatic hyperplasia

BACKGROUND: Benign prostatic hyperplasia (BPH) is an extremely common disease of older men characterized by increased growth of prostatic epithelial and stromal cells. Previously we showed that senescent epithelial cells accumulate in the prostate of aging men and secrete interleukin-1 alpha (IL-1 alpha). IL-8 is also present at increased levels in BPH tissues and induces expression of FGF2, a potent stromal growth factor. Therefore, we sought to determine if IL-8 is also expressed at increased levels by senescent epithelial cells and if this secreted IL-8 plays a role in the pathogenesis of BPH. METHODS: Expression of IL-8 in human BPH tissue and primary cultures of prostatic epithelial cells was analyzed using an enzyme-linked immunoabsorption assay (ELISA). Tissue senescence was assessed by a quantitative assay for senescence-associated beta galactosidase (SA-beta gal). Proliferation of primary and immortalized prostatic epithelial cells in response to IL-8 was determined by counting of cells at intervals after addition of IL-8. RESULTS: Expression of IL-8 is significantly increased in vitro when cultured prostatic epithelial cells undergo senescence. Quantitative assay of BPH tissue extracts revealed that tissue IL-8 levels are correlated with both SA-beta gal activity and prostate weight. IL-8 promotes proliferation of primary and immortalized prostatic epithelial cells in culture. CONCLUSIONS: Senescence of prostatic epithelial cells results in increased expression of IL-8, which can promote proliferation of non-senescent epithelial and stromal cells by direct and indirect mechanisms, and in this manner contributes to the increased tissue growth seen in BPH.