多器官功能不全综合征患者外周血单核细胞炎性细胞因？…

为探讨多器官功能不全综合征或多脏器衰竭的发病机理，对６８例ＭＯＤＳ患者外周血单核细胞分泌肿瘤坏死因子（ＴＮＦ），白细胞介素１（ＩＬ－１）及白细胞介素６（ＩＬ－６）水平进行了动态观察。采用不同细胞因子生长依赖细胞株生长指数（ＭＴＴ法）测定方法，检测ＭＯＤＳ患者发病时及治疗３、５、７、１０及１５天后外周血单核细胞分泌ＴＮＦ、ＩＬ－１及ＩＬ－６水平。结果：ＭＯＤＳ患者发病后外周血单核细胞分泌ＴＮＦ、ＩＬ     

癌症患者血浆细胞因子水平的变化

应用同位素掺入法及酶联法检测癌症患者血浆白细胞介素１、２、６（ＩＬ１、２、６）活性、肿瘤坏死因子（ＴＮＦ）含量。结果表明：癌症患者血浆ＩＬ１、ＩＬ２、ＩＬ６活性均显著低于对照组，而ＴＮＦ含量却显著高于对照组。提示细胞因子水平的异常可能在肿瘤发生过程中起重要作用。     

银屑病sIL—2R和TNFα变化与中医证型的关系

近年来,随着免疫学技术的发展,可溶性白细胞介素２受体（ｓＩＬ２Ｒ）、肿瘤坏死因子（ＴＮＦα）等细胞因子在银屑病发病中的作用日益受到人们的关注。本文采用ＥＬＩＳＡ法检测了６０例银屑病患者血清ｓＩＬ２Ｒ及ＴＮＦα水平,并探讨其与中医辨证分型的关系。１...     

白细胞介素－6在老年女性原发性骨质疏松症发病中的作用

为探讨白细胞介素－６（ＩＬ－６）在老年女性原发性骨质疏松症（ｏｓｔｅｏｐｏｒｏｓｉｓＯＰ）发病中的作用，本文采用ＩＬ－６依赖性细胞株ＭＨ６０．ＢＳＦ增殖反应ＭＴＴ法检测了３０例老年女性骨质疏松性骨折患者和２４例正常者以及１４例健康绝经前女性外周血单核细胞培养上清（ＰＢＭＣ）ＩＬ－６水平以及血清雌激素（Ｅ２）、骨钙素（ＢＧＰ）等水平的变化。结果：绝经后妇女ＩＬ－６水平高于绝经前，而ＯＰ组又高于ＮＯＰ组。以ＯＰ组ＩＬ－６为因变量的多元回归分析发现：ＩＬ－６与年龄无明显相关关系，与前臂骨密度（ＢＭＤ）和Ｅ２呈负相关，与ＢＧＰ和尿钙与尿肌酐比值（Ｃａ／Ｃｒ）呈正相关。结果提示老年女性骨丢失属于高转换型，雌激素水平减少使分泌ＩＬ－６细胞活化，ＩＬ－６分泌增多，从而刺激骨吸收，骨吸收超过骨形成就会导致ＯＰ的发生     

白细胞介素1β、肿瘤坏死因子α在膝关节原发性骨关节病发病中的作用

目的探讨白细胞介素１β（ＩＬ－１β）、肿瘤坏死因子α（ＴＮＦ－α）在膝关节原发性骨关节病（ＯＡ）发病中的作用。方法提取１６例ＯＡ患者（ＯＡ组）、５例对照者（非ＯＡ组）的关节液,采用酶联免疫吸附法（ＥＬＩＳＡ法）测定ＩＬ－１β,生物活性法（ＭＴＴ法）检测ＴＮＦ－α的水平。结果在ＯＡ组关节滑液中,ＩＬ－１β的水平均显著高于对照组（Ｐ＜０００１）;对照组的ＴＮＦ－α未能测出,而ＯＡ组ＴＮＦ－α的检出阳性率为２５％。其次,为进一步探讨滑液中上述细胞因子的产生来源,传代培养膝关节滑膜细胞并用脂多糖（ＬＰＳ）刺激,ＯＡ组（２０例）关节滑膜细胞自发分泌ＩＬ－１β的水平显著高于对照组（５例）,Ｐ＜００５;ＬＰＳ刺激的条件下,ＯＡ组和对照组分泌ＩＬ－１β均显著升高,尤以ＯＡ组为著（Ｐ＜０００１）;ＴＮＦ－α在ＯＡ组中仅有两例呈阳性,对照组中均为阴性。结论ＩＬ－１β和ＴＮＦ－α在骨关节病的发病中起重要作用。ＯＡ患者滑膜细胞高水平自发性分泌ＩＬ－１β可能与其炎症发生与发展密切相关,可能是关节滑液中ＩＬ－１β的主要来源,而滑膜细胞分泌ＴＮＦ－ａ可能不是关节滑液中的主要来源。     

血浆内毒素和细胞因子在腹腔感染致多系统器官功能障碍早期的变化

为观察腹腔感染（ＩＡＩ）致多系统器官功能障碍（ＭＳＯＤ）早期血浆内毒素和细胞因子的变化,在制作ＩＡＩ致ＭＳＯＤ动物模型的基础上,对感染组（行盲肠结扎加穿孔手术）及对照组（行盲肠探查术）兔在实验０、１、２、３、４、５、６及２４小时不同时相的血浆内毒素和细胞因子包括肿瘤坏死因子（ＴＮＦ）、白细胞介素１和６（ＩＬ１,ＩＬ６）进行了检测,并记录动物死亡情况和生存时间。结果显示：感染组血浆内毒素和ＴＮＦ水平在实验后１小时、ＩＬ６在实验后２小时开始显著升高,ＩＬ１无显著变化。感染组兔于１周内均死亡,平均生存时间为８４．１±３９．０小时,对照组兔１周时均存活,两组比较有显著性差异（Ｐ＜０．０５）。本实验所观测到的ＩＡＩ时血浆内毒素及细胞因子的早期变化特点为临床防治研究提供了实验基础。     

白细胞介素1β,肿瘤坏死因子α在膝关节原发性骨关节病发病中 …

目的 探讨白细胞介素１β（ＩＬ－１β）肿瘤坏死因子α（ＴＮＦ－α）在膝关节原发性骨关节病（ＯＡ）发病中的作用。方法 提取１６例ＯＡ患者（ＯＡ组）５例对照者（非ＯＡ组）的关节液,采用酶联免疫吸附法（ＥＬＩＳＡ法）测定ＩＬ－１β,生物活性法（ＭＴＴ法）检测ＴＮＦ－α的水平。结果 在ＯＡ组关节滑液中,ＩＬ－１β的水平均显著高于对照组（Ｐ〈０．００１）,对照组的ＴＮＦ－α未能测出,而ＯＡ组ＴＮＦ－α的检出     

白细胞介素—6在老年女性原发性骨质疏松症发病中的作用

为探讨白细胞介素－６（ＩＬ－６）在老年女性原发性骨质疏松症（ＯＰ）发病中的作用，本文采用ＩＬ－６依赖性细胞株ＭＨ６０．ＢＳＦ增殖反应ＭＴＴ法检测了３０例老年女性骨质疏松性骨折患者和２４例正常者以及１４例健康绝经前女性外周血单核细胞培养上清（ＰＢＭＣ）ＩＬ－６水平以及血清雌激素（Ｅ２）、骨钙素（ＢＧＰ）等水平的变化。结果：绝经后妇女ＩＬ－６水平高于绝经前，而ＯＰ组又高于ＮＯＰ组。以ＯＰ组ＩＬ－６为因     

PGE2和IL-2/IL-2R 在胃癌患者手术前后的动态变化和相互关系

目的　探讨胃癌患者外周血中白细胞介素２ （ＩＬ２）、白细胞介素２ 受体（ｓＩＬ２Ｒ） 水平及ＣＤ２５ 表达三者手术前后的动态变化情况和相互关系,以及前列腺素Ｅ２（ＰＧＥ２） 与ＩＬ２／ＩＬ２Ｒ系统的关系。方法　分别采用ＥＬＩＳＡ法、１２５ＩＲＩＡ法及免疫荧光法对５０ 例胃癌患者手术前后外周血中ＩＬ２、ｓＩＬ２Ｒ、ＰＧＥ２ 水平及ＣＤ２５ 表达进行检测。结果　胃癌患者手术前后外周血中ＩＬ２ 水平及ＣＤ２５ 表达均低于对照组,而ｓＩＬ２Ｒ与ＰＧＥ２ 水平均高于对照组;切除肿瘤后ＩＬ２ 水平及ＣＤ２５ 表达较术前升高,而ｓＩＬ２Ｒ及ＰＧＥ２ 水平较术前下降;６ 例术后发生肿瘤转移或复发的患者中,再次出现ＩＬ２ 水平及ＣＤ２５ 表达下降,而ｓＩＬ２Ｒ及ＰＧＥ２ 水平上升,胃癌患者术前ＩＬ２ 水平与术前ＰＧＥ２ 水平呈显著负相关,术前ｓＩＬ２Ｒ水平与ＩＬ２ 水平亦呈显著负相关。结论　ＰＧＥ２ 与ｓＩＬ２Ｒ 参与了胃癌患者术前存在的免疫抑制过程。非甾体抗炎药（ＮＳＡＩＤ）与外源性ＩＬ２ 联合应用以预防胃癌转移或复发理论上具有可行性。     

急性胰腺炎患者外周血IL-6和sTNFR的变化及其临床意义

目的 探讨炎性细胞因子ＩＬ－６，ＴＮＦα和其拮抗因子ｓＴＮＦＲ水平的变化及其在胰腺炎（ＡＰ）发生、发展和转归中的作用。方法 采用ＥＬＩＳＡ双抗体夹心法检测了轻、重２组共４１例ＡＰ患者发病后第１、５、１４天外周血ＩＬ－６和可溶性肿瘤坏死因子受体（ｓＴＮＦＲ）水平的变化。结果 轻症组２２例患者在发病第５天后逐渐恢复，重症组１９例中１２例在发病后５￣７天病情渐趋好转。两组患者在发病后第１、５、１４天的ｓ     

Haemodialysis membranes modulate chronically the production of TNF alpha, IL1 beta and IL6.

As cytokines may play a role in the adverse effects of haemodialysis, TNF alpha, IL1 beta and IL6 were investigated before the haemodialysis session (chronic effect) and after 30 and 60 min (session effect). We found that haemodialysis exerts a chronic effect on cytokines but the type of haemodialysis membrane, Cuprophan or Hemophan, specifically influences each cytokine. Circulating levels of TNF and unstimulated production of TNF and IL1 by monocytes were increased in patients dialysed with Hemophan, whereas a greater LPS-stimulated production of TNF was observed in patients dialysed with Cuprophan. Both types of membrane induced a higher production of IL6 as compared to controls. The alternate use of Cuprophan and Hemophan demonstrated that the production of TNF and IL1 was dependent on the type of haemodialysis membrane. We also found that Cuprophan induced a reversible decrease of spontaneous and LPS-stimulated production of TNF, IL1 and IL6 during the haemodialysis session. Taken together, these results suggest that Hemophan induced a sustained production of cytokines whereas Cuprophan primed monocytes, probably through the activation of the complement pathway.     

Plasma cytokines after thermal injury and their relationship to infection.

OBJECTIVE: The relationship of plasma cytokine levels to infection, core temperature, and to one another in patients with thermal injury was examined. SUMMARY BACKGROUND DATA: The response to infection has been associated with cytokines such as interleukin 1 beta (IL1 beta), interleukin 6 (IL6), and tumor necrosis factor alpha (TNF alpha), and these cytokines have been studied in various inflammatory diseases. The authors previously reported that patients with thermal injury have elevated IL1 beta and IL6 plasma levels and that these cytokines may play different roles in the response to thermal injury. METHODS: IL1 beta, IL6, and TNF alpha were measured by enzyme-linked immunosorbent assay (ELISA) in serial samples of plasma from 27 patients. RESULTS: IL6 and TNF alpha levels were increased in severely infected patients as compared to patients who remained free of infection, and the IL6 level was higher in infected patients who died than those who survived. There was no apparent relationship between IL1 beta levels and infection. IL6 and IL1 beta were positively correlated with core temperature. The correlations between IL6 and IL1 beta, between IL6 and TNF alpha, and between TNF alpha and IL1 beta were significant. CONCLUSIONS: These results suggest that IL6 and TNF alpha play a role in the response of burned patients to infection.     

他汀药物治疗对尿毒症患者外周血单个核细胞功能的影响

目的：探讨小剂量他汀治疗对尿毒症患者外周血单个核细胞（PBMC）功能的影响。方法：选择尿毒症患者55例,随机分为他汀治疗组（氟伐他汀胶囊,20mg/d）和对照观察组,采用放射免疫法测定患者血清和PBMC培养上清中白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）含量。另选择20例健康人作为正常对照组。结果：与正常组比较,尿毒症患者血清炎症细胞因子（IL-1、IL-6、TNF-α）含量显著升高（P〈0.05）,PBMC分泌上述炎症细胞因子的能力也显著增强（P〈0.05）。与尿毒症患者对照组比较,他汀治疗组患者血清炎症细胞因子水平明显下降（P〈0.05）,PBMC基础分泌和血管紧张素Ⅱ刺激分泌炎症细胞因子的能力被显著抑制（P〈0.05）。小剂量他汀治疗对血糖、血脂（总胆固醇、低密度脂蛋白胆固醇）均无影响。结论：小剂量他汀治疗可显著抑制尿毒症患者外周血PBMC的活化。     

Elevation of serum and urine tumor necrosis factor levels after transurethral resection of the prostate]

BACKGROUND: Recent studies have suggested that inflammatory cytokines are major mediator of the acute phase protein response after surgery. The aim of the present study is to investigate the relationship between the degree of surgical trauma and the change of serum and urine cytokine levels after transurethral resection of the prostate (TUR-P). METHOD: Serum and urine concentrations of tumor necrosis factor-alpha (TNF), interleukin-6 (IL 6), and interleukin-1 (IL 1) were evaluated in 55 patients who underwent TUR-P and in 23 patients who underwent abdominal surgery. The samples were collected periodically before and after an intervention, and the concentrations of cytokines were measured by enzyme-linked immunosorbent assay. RESULTS: The concentration of serum TNF was significantly increased 6 hours after TUR-P. Since serum TNF level was not increased after abdominal surgery, serum TNF level was significantly higher after TUR-P than after abdominal surgery. Serum IL 6 and IL 1 levels were not increased after TUR-P. Urine levels of TNF, IL 6 and IL 1 were significantly increased after TUR-P, meanwhile no significant elevation of urine cytokine levels was recognized in the patients who underwent abdominal surgery. The elevation of urine cytokine levels was thought to be caused by the increased production of cytokines at the surgically resected sites. The urine TNF level after TUR-P was increased related to the resected tissue volume and irrigation fluid volume. The preoperative urinary tract infection caused excessive elevation of the urine TNF level after TUR-P. The urine TNF level after TUR-P also tended to be increased depending on the degree of postoperative pyrexia. CONCLUSION: These results indicate the unique response of TNF to TUR-P. Measurement of serum and urine TNF levels after TUR-P can be a useful index for evaluating the perioperative condition of the patients undergoing TUR-P.     

The down-regulation of IL1α and IL6, in monocytes exposed to extracorporeal photopheresis (ECP)-treated lymphocytes, is not dependent on lymphocyte phosphatidylserine externalization

Extracorporeal photopheresis (ECP) has been successfully used to treat some inflammatory conditions. Following ECP, lymphocytes become apoptotic and untreated monocytes, exposed to post-ECP lymphocytes, reduce proinflammatory cytokine secretion. This study attempted to establish if this monocyte immunosuppression was linked to phosphatidylserine externalization (detected using Annexin V) on the apoptotic lymphocytes. Using density gradient and magnetic separation, lymphocytes were isolated from three cutaneous T-cell lymphoma and nine chronic graft versus host disease (cGvHD) patients pre-ECP and prior to re-infusion (post-ECP). The collected lymphocytes were cultured overnight and Annexin V levels determined. Peripheral blood was taken from the same patient 20 h later and the monocytes were isolated. The 'fresh' monocytes were introduced to each 20 h pre- and post-ECP lymphocyte culture, stimulated with lipopolysaccharide (LPS) and Brefeldin A and subsequently tested for intracellular tumour necrosis factor alpha, interleukin 1 alpha (IL1alpha), IL1beta, IL6 and IL8. For cGvHD patients, the relative levels of IL1alpha and IL6 were reduced in the untreated, LPS-stimulated monocytes exposed to post-ECP lymphocytes. However, the down-regulation of IL1alpha and IL6 did not correlate to levels of Annexin V-positive lymphocytes. ECP-treated lymphocytes can reduce the ability of LPS-stimulated monocytes to produce some proinflammatory cytokines; however, this effect is not dependent on phosphatidylserine externalization.     

The Influence of Recombinant Human Erythropoietin on Tumor Necrosis Factor α and Interleukin-10 Production by Whole Blood Cell Cultures in Hemodialysis Patients

Abstract: Impaired immunological response in hemodialysis (HD) patients, which leads to inappropriate cytokine production, is partially caused by the hyperstimulation of both T lymphocytes and monocytes/macrophages. Recent data suggest that human recombinant erythropoietin (rhEPO) may have an immunological action. The goal of our study was to estimate the influence of rhEPO treatment on the production of the inflammatory cytokine tumor necrosis factor α (TNFα) and antiinflammatory cytokin interleukin-10 (IL-10) in 10 HD patients receiving rhEPO for 6 months. The levels of cytokines were measured in the in vitro cultures of whole blood. The level of IL-10 increased in all treated patients during the therapy, and it was accompanied by a transitory decrease of TNFα. The results of our studies suggest that rhEPO may reduce the inflammatory process by decreasing production of TNF α and increasing production of IL-10.     

Characterization of synovial fluid cytokine profiles in chronic meniscal tear of the knee

Concentrations of pro‐ and anti‐inflammatory cytokines in synovial fluid samples collected from patients with chronic meniscal tears were investigated. An acute inflammatory response is generally reported 24–48 h after knee injury, but the largest body of data available in literature concerns anterior cruciate ligament injury and very little information is available about the balance of soluble factors in the synovial fluid of knees with chronic meniscal tears. Sixty‐nine patients (46 males and 23 females) with meniscal tear that occurred more than 3 months earlier were enrolled. According to cartilage integrity assessment by arthroscopic examination, patients were assigned to one of the following groups: (i) no chondral damage (n = 18); (ii) chondral damage graded from I to II (n = 15); and (iii) chondral damage graded from III to IV (n = 37). In all groups, levels of IL‐10 and inflammatory cytokines IL‐6, TNF‐α, and IL‐8 where greater compared with those reported in the intact population; by contrast, levels of IL‐1ra and IL‐1β were significantly lower. Interestingly, IL‐6 levels were higher in female than male patients. Cytokine levels did not correlate with degree of chondral damage. IL‐6 and IL‐1ra levels positively correlated with IL‐1β, and negatively correlated with TNF‐α. Interestingly, levels of IL‐1β and TNF‐α were inversely correlated. Our data demonstrate increased levels of pro‐inflammatory cytokines (IL‐6, IL‐8, and TNF‐α) in the chronic phase of meniscal trauma. This pro‐inflammatory state is maintained in the joint from the time of initial injury to several months later and could be a key factor in hampering cartilage regeneration. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:340–346, 2017.

     

Acute and late changes in intraarticular cytokine levels following anterior cruciate ligament injury

Surgical reconstruction of the anterior cruciate ligament (ACL) does not necessarily decrease the risk of developing osteoarthritis (OA). The inflammatory response and relative changes in pro‐ and anti‐inflammatory cytokines could participate in triggering the development of OA. To test this hypothesis we measured the concentrations of IL‐1β, IL‐1ra, IL‐6, IL‐8, IL‐10, and TNF‐α at different times after ACL rupture. The sample population consisted of 48 patients with ACL tear which were assigned to different groups according to the time elapsed from the injury: 22 acute (A), 7 early sub‐acute (ESA), 11 late sub‐acute (LSA), and 8 chronic (C). In group A, there were high levels of IL‐1β, IL‐6, and IL‐8, whereas levels of IL‐1ra and TNF‐α were significantly lower than usually reported. IL‐1β and IL‐8 concentrations returned with time to normal levels in the ESA group. Interestingly, IL‐1ra levels remained always significantly lower than normally reported levels, and TNF‐α levels did not increase after trauma. Our data show increased level of pro‐inflammatory cytokines (IL‐6 and IL‐8) in the acute phase of inflammation which could be responsible for triggering cartilage catabolism and suggest that prompt neutralization of IL‐6 and IL‐8 accumulations in synovial fluid could help prevent development of OA in ACL‐injured knees. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 315–321, 2013     

Elevated cytokine production restores bone resorption by human Btk‐deficient osteoclasts

Mutations in Bruton's tyrosine kinase (Btk) cause the B‐cell disorder X‐linked agammaglobulinaemia (XLA) in humans, but the effect of Btk deficiency in human bone health has not been investigated previously. In this study, we show that human Btk‐deficient osteoclasts are defective at resorption activity in vitro owing to a dysregulation of the actin cytoskeletal function. Contrary to expectation, XLA patients did not exhibit increased bone density or alterations in serum markers of bone turnover, indicating that a potential compensation mechanism normalizes bone homeostasis. In contrast to the bone turnover markers, the levels of inflammatory cytokines interleukin 6 (IL‐6), IL‐1β, and tumor necrosis factor α (TNF‐α) were significantly elevated in XLA patients' serum compared with control individuals. Supplementation of osteoclast cultures from normal and XLA subjects with serum from XLA patients or recombinant inflammatory cytokines IL‐6, IL‐1β, and TNF‐α resulted in a stimulation of osteoclast activity in vitro, whereas the addition of cytokine‐neutralizing antibodies inhibited this stimulatory effect, confirming that elevated inflammatory cytokines in XLA serum heightened osteoclast activity in vitro. This study provides novel evidence that Btk signaling is crucial for optimal actin cytoskeletal organization and lacunar resorption in isolated osteoclasts. In XLA patients, however, these inherent osteoclast defects are corrected by increased inflammatory cytokine levels, restoring osteoclast activity and leading to the normalization of bone density. © 2011 American Society for Bone and Mineral Research.     

The isoflavone genistein inhibits LPS-stimulated TNFalpha, but not IL-6 expression in monocytes from hemodialysis patients and healthy subjects

BACKGROUND: Whole blood and peripheral blood mononuclear cells from hemodialysis (HD) patients show increased production and secretion of inflammatory cytokines. We determined the contribution of blood monocytes to the production of inflammatory cytokines in whole blood from HD patients. METHODS: Whole blood and isolated mononuclear cells from HD patients and healthy control subjects were preincubated with the isoflavone genistein and stimulated with LPS. TNFalpha, IL-6 and IL-10 formation in the whole blood was measured with ELISA and intracellular cytokine formation in CD 14-positive monocytes was determined by flow cytometry. RESULTS: Unstimulated blood levels of TNFalpha, IL-6 and IL-10 were significantly elevated in HD patients compared to controls, but intracellular monocyte content of these cytokines was identical between groups. LPS induced a robust TNFalpha response in both whole blood and monocytes, and TNFalpha formation was 2.3-fold higher in blood from HD patients compared to controls. A similar trend was observed in monocytes. Conversely, LPS stimulation increased IL-6 levels >1000-fold in whole blood, albeit without a noticeable difference between groups. Only minor increases in monocyte IL-6 content were observed. The isoflavone genistein did not inhibit IL-6 formation and did not alter basal TNFalpha levels, but genistein selectively blocked LPS-induced TNFalpha formation in whole blood and monocytes from both groups. CONCLUSION: Intracellular levels of TNFalpha, IL-6 and IL-10 in monocytes are indistinguishable between HD patients and healthy controls. However, monocytes from HD patients are selectively primed for enhanced TNFalpha secretion in response to LPS. The selective inhibition of monocyte TNFalpha production by genistein may explain the anti-inflammatory action of this phytochemical observed in vivo.