乌司他丁影响严重脓毒症大鼠IL-10、TNF-α、IL-1β水平的研究

目的探讨乌司他丁(UTI)对细菌性严重脓毒症大鼠血清IL-10、TNF-α、IL-1β水平的调控作用。方法将SD大鼠随机分为生理盐水对照组、氧氟沙星抗感染组、UTI-氧氟沙星抗炎抗感染组和UTI组。每组15只。经腹腔内注射创伤弧菌建立脓毒症模型,15 h后取单侧颈总动、静脉血标本测定血清IL-10、TNF-α、IL-1β的水平。结果UTI-氧氟沙星抗炎抗感染组较氧氟沙星抗感染组、UTI组及生理盐水对照组的TNF-αI、L-1β水平显著降低(P<0.01),IL-10水平差别无统计学意义(P>0.05)。结论UTI能下调致炎因子TNF-α、IL-1β,并对IL-10有一定的上调作用,从而减轻组织器官炎症反应的病理损害而起保护作用,避免全身炎症反应综合征进一步向MODS发展。     

IL-10区域动脉灌注对急性胰腺炎大鼠血浆IL-6和TNF-α的影响

目的探讨IL-10区域动脉灌注(LAI)对急性胰腺炎(AP)大鼠血浆IL-6和TNF-α的影响。方法以5%牛磺胆酸钠胰胆管注射(1 ml/kg)制成大鼠急性胰腺炎模型,IL-10(40 000 UI/kg)LAI,以生理盐水为对照,检测大鼠血浆IL-10I、L-6、TNF-α和淀粉酶。结果假手术组大鼠血浆IL-10测不出,IL-6、TNF-α和淀粉酶分别为(17.5±1.3)pg/ml、(71.25±5.75)pg/ml和(885.4±136.3)U/L,AP大鼠血浆IL-6、TNF-α明显升高,与假手术组对比有显著差异(P<0.05);IL-10 LAI则使AP大鼠血浆3 h和6h的IL-6、TNF-α明显降低,与生理盐水组及AP组对比均有显著差异(P<0.05),但12 h时二者明显升高,与生理盐水组及AP组对比均有显著差异(P<0.05),IL-10LAI使大鼠淀粉酶明显下降。结论IL-10 LAI能降低AP大鼠3 h和6 h时的IL-6、TNF-α,但后期(12 h)则使二者升高,同时能降低AP大鼠淀粉酶,IL-10有望成为AP综合治疗的药物之一。     

急性水肿型胰腺炎IL-1β和TNF-α的变化及大黄素的干预作用

目的探讨大黄素对大鼠急性水肿型胰腺炎的保护作用机制。方法应用蛙皮素制作急性水肿型胰腺炎模型,将30只大鼠随机分为空白对照组、水肿型胰腺炎组和大黄素治疗组。于造模后12 h,采用酶联免疫法(ELISA)和逆转录-多聚酶链反应(RT-PCR)技术检测血清淀粉酶测(AMY)、白介素-1β(I L-1β)和胰腺组织肿瘤坏死因子-α(TNF-α)水平。结果大黄素治疗组胰腺炎组织损伤明显减轻,治疗组血中IL-1β和胰腺组织中TNF-α的含量显著低于胰腺炎组。结论大黄素可能通过抑制IL-1β、TNF-α的产生,从而减轻水肿型胰腺炎症。     

清胰汤对大鼠SAP早期SIRS的影响

目的：观察中药清胰汤对大鼠SAP（重型急性胰腺炎）早期SIRS（全身炎症反应综合征）的影响。方法：选用健康雄性SD大鼠80只，随机分为4组，假手术组（shaln组）、SAP组、地塞米松治疗组（D组）、清胰汤治疗组（Q组），每组20只。采用放免法检测血清TNFα（肿瘤坏死因子α）、IL-1（白介素-1）、IL-6（白介素-6），生化法检测血清AMY（淀粉酶）水平，计算胰腺脏器系数并观察大体及光镜下病理学改变。结果：各组血清TNFα、IL-1、IL-6均明显升高（P〈0．01），并随时间的延长升高更加显著（P〈0．01）。给予清胰汤后，腹水量都明显减少；除2h组外胰腺病理改变明显减轻，胰腺病理评分减少（P〈0．01）；血清AMY、TNFα、IL-1、IL-6明显下降。结论：清胰汤对大鼠SAP早期SIRS具有治疗作用。     

前列腺素E2对急性坏死性胰腺炎大鼠IL-10、TNF-α及IL-1β的调控和对肺组织损伤的影响

目的:探讨前列腺素E2(PGE2)对大鼠急性坏死性胰腺炎(ANP)中血清白介素-10(IL10)、肿瘤坏死因子(TNF-a)以及白介素-1β(IL-1β)的含量及肺组织损伤的影响.方法:将SD大鼠91只随机分4组:假手术对照组(n=7),ANP组(n=28),PGE2前处理组(n=28),PGE2后处理组(n=28);观察同组不同时间,不同组同时间的IL-1β、TNF-α和IL-10的动态变化,并观察各组肺组织的病理切片.结果:各指标在1 h、3 h、6 h和12hPGE2前处理组和PGE2后处理组与ANP组相比较差异有显著性(P＜0.01),在PGE2前处理组,TNF-α、IL-1β下降更加明显,IL-10升高两组都很明显,而且有PGE2保护的两组,其肺组织损伤出现较迟、较轻.结论:IL1β和TNF-α在大鼠ANP的全身性反应过程中起重要的递质作用,IL-10能抵抗它们的作用.PGE2能降低ANP大鼠血清中IL-1β、TNF-a含量,提高IL-10含量,减轻肺组织损伤.     

丙泊酚对内毒素性急性肺损伤大鼠血清TNF-α、IL-1β及IL-10的影响

目的探讨内毒素性急性肺损伤(ALI)大鼠用丙泊酚后处理对血清肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-10影响。方法雄性SD大鼠96只,随机均分为四组,每组24只。脂多糖(LPS)致伤组(B组)、丙泊酚低剂量治疗组(C组)和丙泊酚高剂量治疗组(D组)经尾静脉注射LPS 5 mg/kg制作ALI模型;之后生理盐水对照组(A组)和B组泵入生理盐水,C、D组分别注射丙泊酚2、4 mg/kg后再分别泵入4、8 mg.kg-1.h-1。分别在制模后1、2、3、4 h抽取动脉血测定TNF-α、IL-1β及IL-10的水平。结果制模后各时点A组大鼠TNF-α、IL-1β和IL-10含量均明显低于其它三组(P<0.05或P<0.01)。制模后1、2 h B组TNF-α、IL-1β和IL-10含量明显高于C、D组(P<0.01),C组IL-1β和IL-10含量明显高于D组(P<0.05或P<0.01)。制模后3、4 h B组IL-1β和IL-10含量仍明显高于C、D组(P<0.01),C组显著高于D组(P<0.01)。结论丙泊酚可以显著抑制ALI大鼠血清TNF-α、IL-1β及IL-10上升的程度。     

骨肿瘤患者血清细胞因子TNF-α和IL-6水平观察及临床意义

目的探讨骨肿瘤患者血清中TNF-α和IL-6的变化及临床意义。方法采用ELISA法测定45例骨肿瘤患者和40例健康对照人血清中TNF-α和IL-6水平。结果骨肿瘤患者TNF-α和IL-6活性水平均高于健康组（P〈0.01）,骨转移患者（伴淋巴结转移）TNF-α和IL-6水平均高于骨肿瘤患者（P〈0.05）。结论血清中TNF-α和IL-6活性水平可能与骨肿瘤发生、发展有关。测定其水平可作为临床病情观察和监测疗效的辅助手段。     

银杏叶提取物对重症急性胰腺炎大鼠脑组织中IL-1β、IL-6和TNF-α表达水平的影响

目的观察银杏叶提取物(ginkgo biloba extract,GBE)对重症急性胰腺炎(severe acute pancreatitis,SAP)大鼠胰腺及脑组织中IL-1β、IL-6及TNF-α表达水平的影响,探讨SAP脑损害的发病机理及GBE对脑损害的治疗效果。方法 54只Winstar大鼠随机分为正常对照组、模型组及治疗组3组,每组18只。正常对照组开腹仅翻动胰腺;治疗组及模型组采用胰腺被膜下注射5%牛黄胆酸钠法制作SAP模型,每隔8 h分别于腹腔内注射GBE和生理盐水。制模后6、12及24 h时段各组取材,测定血清淀粉酶值,光镜下行胰腺组织病理评分,免疫组化法测定胰腺和脑组织中IL-1β、IL-6和TNF-α的表达水平。结果血清淀粉酶值及胰腺组织病理评分值治疗组较模型组降低(P<0.01)。24 h与6及12 h时段比较,胰腺组织中IL-1β、IL-6和TNF-α表达水平,在模型组增高(P<0.05或P<0.01),在治疗组无明显变化(P>0.05);脑组织中IL-1β、IL-6和TNF-α表达水平,在模型组增高(P<0.05或P<0.01),在治疗组降低(P<0.05或P<0.01)。同时段比较,IL-1β、IL-6和TNF-α表达水平治疗组均较模型组降低(P<0.01)。结论 SAP时胰腺和脑组织中IL-1β、IL-6及TNF-α的表达明显增加,GBE对SAP时胰腺及脑组织中IL-1β、IL-6和TNF-α有抑制清除作用。     

大黄素对腹腔感染大鼠血浆白蛋白及TNF-α、IL-6影响的实验研究

目的：探讨大黄素对于腹腔感染大鼠的保护作用。方法：90只大鼠随机分为3组，A组：假手术组；B组：大黄素治疗组；C组：盲肠结扎穿孔模型（CLP）组。造模12h，2，4h，36h后分别测定血浆白蛋白浓度、肿瘤坏死因子-α（TNF—α）、白介素-6（IL-6）等并观察肠粘膜损伤程度。结果：CLP后大鼠血浆白蛋白浓度降低，而C组下降较B组明显（P〈0．05）。TNF—α、IL-6明显升高，而C组升高较B组明显（P〈0．01），肠粘膜损伤评分变化也有相同趋势（P〈0．05）。结论：大黄素能减轻CLP所致腹腔感染大鼠的炎症反应和肠粘膜的损伤。     

Comparison of systemic cytokine levels in patients with acute respiratory distress syndrome, severe pneumonia, and controls

BACKGROUND: The inflammatory response has been widely investigated in patients with acute respiratory distress syndrome (ARDS) and pneumonia. Studies investigating the diagnostic values of serum cytokine levels have yielded conflicting results and only little information is available for the differential diagnosis between ARDS and pneumonia. METHODS: Clinical and physiological data, serum concentrations of tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, and quantitative cultures of lower respiratory tract specimens were obtained from 46 patients with ARDS and 20 with severe pneumonia within 24 hours of the onset of the disease and from 10 control subjects with no inflammatory lung disease. Cytokine concentrations were compared between groups and determinants in addition to the diagnosis were tested. RESULTS: Serum TNF-alpha levels were significantly higher in ARDS patients (67 (57) pg/ml) than in patients with severe pneumonia (35 (20) pg/ml; p = 0.031) or controls (17 (8) pg/ml; p = 0.007). For IL-1beta and IL-6 the observed differences were not statistically significant between patients with ARDS (IL-1beta: 34 (65) pg/ml; IL-6: 712 (1058) pg/ml), those with severe pneumonia (IL-1beta: 3 (4) pg/ml, p = 0.071; IL-6: 834 (1165) pg/ml, p = 1.0), and controls (IL-1beta: 6 (11) pg/ml, p = 0.359; IL-6: 94 (110) pg/ml, p = 0.262). TNF-alpha (standardised coefficient beta = 0.410, p<0.001) and IL-1beta (standardised coefficient beta = 0.311, p = 0.006) were most strongly associated with the degree of lung injury, even when the diagnostic group was included in the statistical model. CONCLUSIONS: Serum TNF-alpha levels were higher in patients with ARDS than in those with severe pneumonia or in control subjects. Multivariate results suggest that the levels of systemic TNF-alpha and IL-1beta reflect the severity of the lung injury rather than the diagnosis.     

急性呼吸窘迫综合征病人肺泡表面活性物质的变化

目的　研究患急性呼吸窘迫综合征 (ARDS)时病人肺泡表面活性物质的变化。方法　应用薄层色谱法测定ARDS早期病人 ( 5例 )和晚期病人 ( 5例 )肺泡灌洗液中肺泡表面活性物质 ,并和正常对照组 ( 5例 )作比较。结果　肺泡表面活性物质的含量在对照组、早期组、晚期组分别为6 7 6± 7 2、44 0± 7 3、31 3± 6 5 μg/ml肺灌洗液 ,呈递减改变。肺泡表面活性物质主要活性成份磷脂酰胆碱、磷脂酰甘油和二磷脂酰甘油的百分比在ARDS早期升高 ,分别达 5 6 2 %± 2 8%、9 2 %±1 5 %和 2 9%± 0 7%。在ARDS晚期 ,上述三种活性成份分别降至 39 7%± 5 2 %、5 6 %± 0 7%和 2 6 %± 0 6 %。结论　ARDS病人随着病情的进展加重 ,其肺泡表面活性物质的含量和主要活性成份逐渐减少。提示若使用外源性肺泡表面活性物质防治ARDS ,不仅要在数量上补足 ,而且需要恢复活性成份的比例 ,才有可能获得理想的疗效     

Serum levels of IL-1 beta,TNF-alpha,IL-8, and acute phase proteins in seronegative spondyloarthropathies

OBJECTIVES: Some immunological abnormalities have been described in seronegative spondyloarthropathies (SpA). The aim of this study is to determine the serum levels of IL-1beta, TNF-alpha and IL-8, which are proinflammatory cytokines in active and inactive patients with SpA, to compare the results with those of controls and to investigate a relationship with clinical activity and acute phase proteins. METHODS: Forty-two patients (34 males and eight females) and 22 healthy controls (17 M and 5 F) were included in the study. All patients fulfilled Amor criteria for the classification of SpA. Among patients 23 had active and 19 had inactive disease. IL-1beta, TNF-alpha and IL-8 were determined by enzyme-linked immunosorbent assay ( ELISA), acute phase proteins were measured by nephelometric assay. RESULTS: There was no statistically significant difference between mean IL-1beta levels of patient groups and controls. Serum mean TNF-a levels in active and inactive patients were significantly increased as compared to that in the controls (P < 0.05, P < 0.05, respectively). Serum mean IL-8 levels in active patients was significantly increased as compared to that in the controls and in inactive patients (P < 0.01, P < 0.01, respectively). High serum IL-8 levels correlated well with C-reactive protein and haptoglobulin, but there was no correlation between IL-1beta or TNF-alpha levels and acute phase proteins such as C-reactive protein, alpha-1 acid glycoprotein, alpha-1 antitrypsin and haptoglobulin. CONCLUSIONS: These results suggest that serum IL-8 may reflect clinical activity of the disease and may be helpful for monitoring patients with SpA.     

Diagnostic studies in patients with acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a clinical-radiological diagnosis. Clinical diagnosis comprises severe hypoxemia assessed by arterial oxygen tension/fraction of inspired oxygen ratio of less than 200 and bilateral infiltrate on a chest radiograph in the absence of left atrial hypertension. The sensitivity and specificity of the clinical diagnosis vary based on the underlying etiology for ARDS. Except for presence of bilateral infiltrate on chest radiograph and severe hypoxemia on arterial blood gas, most diagnostic studies are used to exclude mimics of ARDS and potentially modify treatment. Computerized tomography of the chest is helpful in understanding the extent of the disease and is more sensitive in identifying pneumomediastinum and pneumothoraces seen frequently in patients with ARDS, which can be missed on a chest radiograph, especially if they are small in size. Measurements of alveolar dead space ventilation fraction can be helpful in determining the prognosis in individuals with ARDS. Bronchoalveolar lavage, transbronchial lung biopsy, and open lung biopsies can be safely performed in patients with ARDS. Bronchoalveolar lavage fluid in patients with ARDS shows neutrophil predominance with increased edema fluid to serum protein ratio. Diffuse alveolar damage, a pathognomic of ARDS, is seen on histopathology on transbronchial lung biopsy or open lung biopsy. Most common complications of these procedures include transient hypoxemia, respiratory acidosis, and pneumothorax with occasional persistent air leak. The potential risk of diagnostic studies should be balanced against the possible foreseeable benefits of the diagnostic studies.     

Whole blood production of monocytic cytokines (IL-1beta, IL-6, TNF-alpha, sIL-6R, IL-1Ra) in haemodialysed patients.

BACKGROUND: The production of monocytic cytokines by isolated mononuclear cells after stimulation by phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) is generally increased in haemodialysed (HD) patients. We performed whole blood (WB) cultures to evaluate cytokine production by blood cells inside their complex cellular and humoral network. METHODS: Diluted whole blood from HD patients (collected before dialysis) and controls was cultured alone with PHA (2.5 microg/ml) or LPS (1 and 3 microg/ml). Supernatants were collected after 24 and 48 h of culture, and concentrations of IL-1 beta, IL-6, TNF-alpha, sIL-6R and IL-1Ra were determined by ELISA. RESULTS: The low spontaneous production of IL-1beta, IL-6 and TNF-alpha in both patients and controls was not significantly modified by PHA. The lower dose of LPS (1 microg/ml) induced a significant but lower increase in production of IL-1beta, IL-6 and TNF-alpha in patients than in controls. In contrast, while it did not further increase their production in controls, the higher concentration of LPS (3 microg/ml) still increased their production in patients to the same level than in controls. The plasma concentrations of sIL-6R were higher in patients than in controls. In both groups, the sIL-6R concentration did not vary during the culture period whether the cells were stimulated or not with LPS or PHA. This suggests that the increased plasma levels of sIL-6R were not produced by blood cells. Despite a similar significant LPS and PHA induced production of IL-1Ra, the IL-1Ra/IL-1beta ratio was always higher in patients than in controls. CONCLUSION: Monocytes from HD patients in WB cultures are hyporesponsive to PHA and LPS for their IL-1beta, TNFalpha and IL-6 production in contrast to isolated monocytes that demonstrate signs of activation. If it reflects the in vivo situation it could partly explain the immune defect in uraemic and haemodialysed patients. Higher sIL-6R/IL-6 and IL-1Ra/IL-1beta ratios could also participate to the complex immune disturbances of HD patients by reducing the biological activity of two cytokines playing a major role in the immune and inflammatory network.     

Protective ventilation of patients with acute respiratory distress syndrome

The majority of patients with acute respiratory distress syndrome(ARDS) require mechanical ventilation. This support providestime for the lungs to heal, but the adverse effects of mechanicalventilation significantly influence patient outcome. Traditionally,these were ascribed to mechanical effects, such as haemodynamiccompromise from decreased venous return or gross air leaks inducedby large transpulmonary pressures. More recently, however, theARDS Network study has established the clinical importance oflowering the tidal volume to limit overdistension of the lungwhen ventilating patients with ARDS. This study suggests thatventilator-associated lung injury (VALI) caused by overdistensionof the lung contributes to the mortality of patients with ARDS.Moreover, the results from clinical and basic research haverevealed more subtle types of VALI, including upregulation ofthe inflammatory response in the injured and overdistended lung.This not only damages the lung, but the overflow of inflammatorymediators into the systemic circulation may explain why mostpatients who die with ARDS succumb to multi-organ failure ratherthan respiratory failure. The results of these studies, thepresent understanding of the pathophysiology of VALI, and protectiveventilatory strategies are reviewed. Br J Anaesth 2004; 92: 261–70     

Protective ventilation of patients with acute respiratory distress syndrome

Editor—We read with interest the review article by Moloneyand Griffiths¹ on protective ventilation of patients with acuterespiratory distress syndrome (ARDS). Recent insights into pulmonarymechanics have led to a re-evaluation of the role of positiveend-expiratory pressure (PEEP) in ventilated ARDS patients.We felt that the authors did not highlight this issue correctly.In their review, the