Central tumour necrosis factor-α mediates the early gastrointestinal motor disturbances induced by lipopolysaccharide in sheep

Cytokines are involved in fever and other symptoms of the acute phase response induced by endotoxins. The aim of this work was to study the involvement of central tumour necrosis factor-alpha (TNF-alpha) in the changes induced by lipopolysaccharide (LPS) on gastrointestinal (GI) motility in sheep. Body temperature and myoelectric activity of the antrum, duodenum and jejunum was recorded continuously. Intravenous (i.v.) administration of LPS (0.1 micro g kg-1)-induced hyperthermia, decreased gastrointestinal myoelectric activity and increased the frequency of the migrating motor complex (MMC). These effects started 40-50 min after LPS and lasted for 6-7 h. TNF-alpha (50 and 100 ng kg-1) mimicked these effects when injected intracerebroventricularly (i.c.v.) but not i.v. Pretreatment with soluble recombinant TNF receptor (TNFR:Fc, 10 micro g kg-1, i.c.v.) abolished the TNF-induced actions and reduced those evoked by LPS. Furthermore, the effects induced by either LPS or TNF were suppressed by prior i.c.v. injection of indomethacin (100 micro g kg-1). In contrast, the i.v. injections of TNFR:Fc or indomethacin were ineffective. Our data suggest that LPS disturbs GI motility in sheep through a central pathway that involves TNF-alpha and prostaglandins sequentially.     

Differential control of mesangial cell proliferation by interferon-gamma.

Rat mesangial cells were shown to be sensitive to recombinant interferon-gamma (IFN-gamma). IFN-gamma reduced thymidine uptake by these cells and inhibited cell proliferation. Incubation of the cells with 1000 U/ml IFN-gamma decreased thymidine uptake by up to 64% and cell numbers were decreased by 17%. The effects of IFN-gamma were dose and time dependent and were partially reversible by the anti-IFN-gamma monoclonal antibody DB-1. This lymphokine did not reduce incorporation of RNA and protein precursors however. Measurements of 3H-uridine and 3H-leucine incorporation indicated significant increases in RNA and protein synthesis (37% and 45%, respectively) on a per cell basis. The mitogenic effects of IL-1 and platelet-derived growth factor (PDGF) were also susceptible to IFN-gamma-mediated inhibition but the mitogenic response to epidermal growth factor (EGF) was much less sensitive. We conclude that while IFN-gamma may act to modulate the mitogenic signals provided by some factors such as IL-1 and PDGF, the response to EGF appears to be unaffected.     

Involvement of platelet-activating factor and tumour necrosis factor in the pathogenesis of joint inflammation in rabbits.

We have studied the participation of platelet-activating factor (PAF) in antigen-induced arthritis in rabbits, as well as the possible co-operation between PAF and tumour necrosis factor (TNF) in their ability to induce joint inflammation when injected into the knees of healthy rabbits. The administration of two structurally different PAF receptor antagonists, BN52021 and Alprazolam, from 4 h before the intra-articular injection of ovalbumin in preimmunized rabbits, induced an important reduction in the synovial fluid volume, in the amount of cells infiltrating the articular cavity and the synovial membrane, as well as in the prostaglandin E2 (PGE2) concentration. Furthermore, proteoglycans of the articular cartilage, which were found diminished in animals with non-treated arthritis, were well preserved in rabbits treated with PAF antagonists. All the synovial fluids from joints with arthritis had detectable amounts of PAF. The injection of either TNF or PAF into the joints of normal rabbits induced a mild inflammation. When TNF was administered 1 h before PAF, a synergistic response was noted in the synovial fluid volume, in the accumulation of leucocytes, and in the amount of PGE2. The administration of BN50726, a hetrazepine with a potent PAF-receptor antagonist effect, induced a diminution in those parameters. Our results suggest that PAF may be an early and important mediator of joint damage, and that TNF can amplify the inflammatory response induced by PAF. PAF receptor antagonists could play some role in the treatment of inflammatory joint diseases.     

Splanchnic ischaemia and its role in multiple organ failure

Multiple organ failure remains the leading cause of death in the intensive care unit. Increasing numbers of investigators have focused their attention on the role of gastrointestinal tract in the pathogenesis of this syndrome. Their data indicate that inadequate gut perfusion leads to a measurable imbalance between oxygen delivery and the needs of the tissues, i.e., ischaemia. Gut ischaemia of sufficient duration impairs gastrointestinal tract barrier function, facilitating the passage of enteric bacterial endotoxin into the circulation. It has been hypothesized that production of tumor necrosis factor α, and other biologic mediators by endotoxin–stimulated macrophages, triggers a generalized and uncontrolled inflammatory response that ultimately leads to multiple organ failure.
Preliminary evidence suggests that survival can be improved significantly if gut ischaemia is promptly identifed and aggressively treated by administration of fluids and inotropic drugs, using gastric intramucosal pH as the therapeutic endpoint. Future studies are needed to determine whether additional treatment modalities can improve outcome once the inflammatory response has fully developed.     

The influence of erythropoietin on cytokines in haemodialysis patients

Summary: In this study, the administration of erythropoietin to haemodialysis patients revealed its immunomodulating properties. to dissociate the immunological effects of erythropoietin action from its haematological effects the patients in our study were administered recombinant human erythropoietin (rhEpo) at the doses that would not affect erythropoiesis. After baseline data had been obtained, six haemodialysis patients were given rhEpo (Eprex-Cilag) at the dose 7-10 U/kg bodyweight/s.c., three times a week, for 12 weeks. All patients maintained a stable haemoglobin concentration; no blood transfusions were required. Serum levels of tumour necrosis factor (TNF), IL-2 and IL-6 levels of the study patients and the four control patients, not receiving rhEpo, were monitored every 2 weeks. the levels of IL-6 and TNF remained unchanged; however, a low serum level of IL-2, recorded before therapy, increased gradually for 10 weeks until it reached the values observed in normal healthy humans (P<0.01). After that it dropped to the initial values. During the study the red blood cell numbers did not change. This study supports the thesis that erythropoietin administered to haemodialysis patients not only corrects anaemia but also independently modulates immunological response.     

特布他林对海水淹溺型肺水肿兔肺组织炎症反应的抑制作用

目的探讨特布他林对海水淹溺型肺水肿兔肺组织炎症反应的影响。方法36只机械通气的麻醉新西兰兔随机分成正常组（N组）、对照组（C组）和特布他林治疗组（T组）。C组和T组经颈动脉注入4ml／kg的配方海水，20min后C组经颈动脉注入2ml生理盐水，而T、组则注入0．15mg／kg特布他林，N组除未注入配方海水外，其余处理同C组。观察肺泡灌洗液（BALF）中TNF-α计量和中性粒细胞计数，取部分右下肺常规病理学检查，并分别用RT-PCR和ELISA检测肺组织中TNF-α、IL-1β和IL-8的mRNA表达及蛋白含量。结果病理学观察显示C组的肺组织内有大量的炎性细胞浸润，肺泡隔断裂、肺泡破裂、相互融合、肺泡大量萎陷，肺泡内有出血及透明膜形成。T组的上述改变轻于C组。T组肺组织内TNF-α、IL-1β和IL-8的mRNA表达及蛋白含量均显著低于C组（P〈0．05），BALF中TNF-α和中性粒细胞计数减少。结论特布他林可以抑制海水淹溺型肺水肿兔肺组织的TNF-α、IL-1β和IL-8，从而减轻肺组织炎症反应。     

聚乙烯颗粒对人单核细胞分泌促炎因子与抗炎因子的影响

[目的]探讨聚乙烯颗粒对人单核细胞分泌促炎因子与抗炎因子的影响.[方法]用Ceridust 3615 颗粒(聚乙烯颗粒)(平均直径14.27,6.39,1.74,1.01,0.54和0.28 μm)分别刺激人单核细胞,颗粒体积与细胞数的比例为100:1和10:1.在颗粒刺激细胞24 h后,运用ELISA检测培养上清液中的促炎因子(白介素-1β,白介素-6和细胞坏死因子α)及抗炎因子(白介素-10)的表达.[结果]Ceridust 3615 颗粒可刺激单核细胞分泌白介素-1β(IL-1β)、白介素-6(IL-6)和细胞坏死因子α(TNFα),但未能引起白介素-10(IL-10)的表达.颗粒比例增高可促使单核细胞分泌更多的IL-6和TNFα,却减少IL-1β分泌,对IL-10的分泌则无影响.个体差异使巨噬细胞对同种颗粒的刺激产生不同的反应,其差异可达到30倍.[结论]个体差异是影响人工关节寿命的重要因素,聚乙烯颗粒可刺激单核细胞产生炎因子但对产生抗炎因子(IL-10)的作用不明显,提示促炎因子与抗炎因子的不平衡或许是人工关节松动不断进展的另一重要因素.     

Production of multiple cytokines by cultured human melanomas*

Abstract We screened a panel of 8 primary and 21 metastatic melanoma cell lines for constitutive secretion of cytokines. Melanomas expressed bioactivity for TGF-β (8/25 lines) and IFN (7/12), but not IL-2. Immu-noassays detected IL-1α (4/25), IL-1β (12/25), 1L-6 (13/29), IL-8 (29/ 29), TGF-β₂, (5/12) and GM-CSF (11 /29). but not IL-3, IL-4, TNF-α, or IFN-γ. There was no preferential association of cytokine production with cells cultured from primary versus metastatic disease, and only IL-8 was produced by all lines tested. These data demonstrate that cultured melanomas produce a variety of cytokines which are potentially capable of influencing tumor growth in vivo.     

重性抑郁障碍患者躯体症状与脑源性神经营养因子和炎性因子的相关性研究

背景 大量证据表明抑郁障碍患者的躯体症状的风险比正常人高,但躯体易感性的机制尚不明确。部分研究认为前者脑源性神经营养因子前体(ProBDNF)、炎性因子水平比正常人高,而这是否与伴随的躯体症状有关还没有明确的结论。目的 探讨重性抑郁障碍(MDD)患者躯体症状与脑源性神经营养因子(BDNF)、炎性因子的特征及其相关性。方法 选取2019年2月至2020年12月山西医科大学第一医院精神卫生科门诊或住院部MDD患者59例与同期社区招募的健康志愿者32例作为研究对象。根据躯体化症状自评量表(SSS)将MDD患者分为伴躯体症状抑郁障碍(SD)组37例(SSS总分>36分)和不伴躯体症状抑郁障碍(NSD)组22例(SSS总分≤36分),32例健康志愿者为健康对照组(HC组)。收集临床资料,包括性别、年龄、受教育年限、17项汉密尔顿抑郁量表(HAMD-17)评分、SSS评分、BDNF、ProBDNF与炎性因子[C反应蛋白(CRP)、白介素4(IL-4)、白介素6(IL-6)、白介素10(IL-10)、白介素18(IL-18)、白介素23a(IL-23a)、高迁移率族蛋白B1(HMGB1)、肿瘤...