肾病综合征患者白细胞介素-6和可溶性受体的测定及其临床意义

目的　探讨肾病综合征患者白细胞介素 6(IL 6)及其可溶性受体水平变化的临床意义。方法　采用酶联免疫吸附分析法 (ELISA)测定 3 5例肾病综合征患者血清IL 6及其可溶性受体 (sgp13 0、sgp80 )的水平。 结果　肾病综合征活动组血清IL 6、sgp13 0、sgp80浓度明显高于病情缓解组及对照组 (P均 <0 .0 0 1) ;缓解组血清IL 6、sgp13 0、sgp80浓度显著高于对照组 (P <0 .0 0 1)。血sgp13 0、sgp80水平和血肌酐呈正相关 (rsgp80 =0 .68,P <0 .0 1;rsgp13 0 =0 .5 5 ,P <0 .0 5 )。结论　IL 6、sgp13 0和sgp80在肾病综合征发病过程中异常升高 ,且sgp13 0、sgp80浓度升高可作为判断肾小球活动性病变和 (或 )肾功能恶化的参考指标。     

Pathophysiology of large vessel vasculitis and utility of interleukin-6 inhibition therapy

Abstract

Takayasu arteritis (TAK) and giant cell arteritis (GCA) affect mainly large- and medium-sized arteries. In refractory cases, vascular remodeling progresses and leads to serious outcomes. Studies have demonstrated that cytokines such as interleukin (IL)-6 play crucial roles in the pathophysiology of TAK and GCA. Recently, randomized controlled trials on IL-6 inhibition therapy using tocilizumab (TCZ) were performed, and significant effects were exhibited. The purposes of conventional treatments have been to improve symptoms and decrease the levels of inflammatory markers. Arterial changes have been considered as damages. However, after TCZ came into practical use, establishment of treat to target is desired to prevent vascular remodeling. In contrast, a combination therapy of glucocorticoids (GCs) and TCZ notably increases the risk of infections. When TCZ is used, careful attention must be paid to possible infections, and dose of GC should be tapered as much as possible. Future tasks are to establish indication and dosage of TCZ, indication for discontinuation of TCZ due to remission, efficacy of TCZ monotherapy, and protocols of TCZ for pediatric cases.     

川崎病患儿血清可溶性白细胞介素-2受体和白细胞介素-6的变化及意义

目的探讨血清可溶性白细胞介素-2受体(sIL-2R)和白细胞介素-6(IL-6)水平在川崎病(K D)患儿中的变化,及其在发病中的作用。方法采用酶联免疫吸附试验(ELISA)双抗夹心法测定血清sIL-2R和IL-6水平;利用德灵BN ProSpec特种蛋白分析仪检测血清超敏C反应蛋白(hs-CRP)水平。结果30例KD患儿大剂量丙种球蛋白静脉滴注前(静丙前)和滴注后(静丙后)血清slL-2R和hs-CRP水平与对照组比较差异均有统计学意义(P<0.01),静丙前和静丙后比较差异有统计学意义(P<0.01);静丙前KD患儿血清IL-6和对照组比较差异有统计学意义(P<0.01);KD患儿血清slL-2R与hs-CR P水平呈正相关(r=0.6,P<0.01),静丙前K D患儿血清IL-6和hs-CRP呈正相关(r=0.68,P<0.01)。结论血清IL-6和slL-2R参与了川崎病的发生,它们可作为判断预后、评估患儿免疫功能状况的参考指标。     

外周穿刺中心静脉导管在胃肠癌FOLFOX6化学治疗方案中的临床应用

目的探讨外周穿刺中心静脉导管(PICC)在胃肠癌FOLFOX6化学治疗方案中的临床应用.观察其疗效和不良反应.方法 59例胃肠癌行FOLFOX6方案化学治疗患者,采用经外周静脉中心静脉置管(PICC)结合便携式化学治疗泵给药.方案为:奥沙利铂100 mg/m2静脉点滴2 h,第1天;亚叶酸钙400 mg/m2静脉点滴2 h,第1天;5-氟脲嘧啶(5-FU)400 mg/m2静推,第1天;后以5-FU 2.4 g/m2,入化学治疗泵持续静脉输注46 h,每2周重复.结果全组有效率49.2%(29/59),完全缓解10例、部分缓解19例、稳定17例、疾病进展13例.不良反应主要是外周神经炎、胃肠道反应、骨髓抑制,所有反应在停止治疗后可恢复.平均PICC置管时间为62 d;其中10.2%出现静脉炎,3.4%出现导管堵塞,6.8%出现导管移位,未出现严重相关并发症.结论胃肠癌患者采用经PICC管结合化学治疗泵FOLFOX6方案化学治疗,不仅提高化学治疗效果,降低不良反应,同时提高患者生活质量,值得临床推广.     

Circulating levels of interleukin-6, its soluble receptor and interleukin-6/interleukin-6 receptor complexes in patients with type 2 diabetes mellitus

We evaluated the relationship between plasma fibrinogen concentration and the serum levels of interleukin-6 (IL-6), its soluble receptor, and their complex in patients with type 2 diabetes mellitus. The study comprised 57 patients with type 2 diabetes and 15 normal healthy controls. Serum levels of IL-6, soluble IL-6 receptor (IL-6R), and circulating IL-6/IL-6R complex were determined by enzyme-linked immunosorbent assays. Correlations between the different study parameters and serum IL-6, IL-6R, or IL-6/IL-6R complex levels were determined by multiple linear regression analysis. Any association between the different study parameters and the serum levels of IL-6, IL-6R, or IL-6/IL-6R complex were determined by stepwise linear regression analysis. The serum IL-6 level in diabetic subjects was significantly higher than in normal healthy controls (3.48 ± 3.29 pg/ml vs 0.784 ± 0.90 pg/ml, mean ± SD, respectively, P = 0.0001). The specific optical density of the serum IL-6/IL-6R complex in diabetic patients was also significantly higher than in normal healthy controls, although there was no significant difference in the serum IL-6R level between diabetic patients and controls. The serum IL-6 concentration was correlated significantly with the HbA_1C level (β = 0.58, P = 0.04) by multiple regression analysis. Stepwise regression analysis revealed that the levels of serum IL-6 (F = 8.251), HbA_1C (F = 1.08), and serum urea nitrogen (F = 5.603) were associated with the plasma fibrino gen concentration. These results suggest that hyperglycaemia and increased levels of serum IL-6 can increase the plasma fibrinogen concentration, one of the known risk factors for atherosclerosis in patients with type 2 diabetes mellitus. Received: 24 August 1998 / Accepted in revised form: 2 February 1999     

Circulating interleukin-6 and interleukin-6 receptors in patients with acute and recent myocardial infarction

Interleukin-6 (IL-6), a proinflammatory cytokine, plays a key role in the pathogenesis of coronary artery disease (CAD). We investigated circulating IL-6 and its receptors in patients with CAD. We evaluated 39 Japanese patients with CAD (30 males and 9 females aged 36-79 years), measuring their plasma levels of IL-6 and IL-6 receptors alpha and beta (IL-6R alpha, IL-6R beta). Circulating levels of IL-6, IL-6R alpha and IL-6R beta were measured by an enzyme-linked immunosorbent assay. Blood was sampled immediately after admission and again after 1, 2, 3, 6 and 9 h, then every 12 h for 5 days. Atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) were measured on day 3 after symptom onset. Plasma levels of IL-6 and IL-6Rs were significantly increased in 28 patients with acute myocardial infarction (AMI) compared with 15 normal controls. However, neither IL-6 nor IL-6Rs showed an increase in 6 patients with angina pectoris. We observed two peaks for circulating IL-6 in AMI, the first of which showed a significant correlation with ANP as well as BNP. These results may help to explain why the amount of IL-6 produced is closely related to the severity of myocardial dysfunction in patients with CAD.     

Targeted inhibition of interleukin-6 with CNTO 328 sensitizes pre-clinical models of multiple myeloma to dexamethasone-mediated cell death

Interleukin (IL)-6-mediated signalling attenuates the anti-myeloma activity of glucocorticoids (GCs). We therefore sought to evaluate whether CNTO 328, an anti-IL-6 monoclonal antibody in clinical development, could enhance the apoptotic activity of dexamethasone (dex) in pre-clinical models of myeloma. CNTO 328 potently increased the cytotoxicity of dex in IL-6-dependent and -independent human myeloma cell lines (HMCLs), including a bortezomib-resistant HMCL. Isobologram analysis revealed that the CNTO 328/dex combination was highly synergistic. Addition of bortezomib to CNTO 328/dex further enhanced the cytotoxicity of the combination. Experiments with pharmacologic inhibitors revealed a role for the p44/42 mitogen-activated protein kinase pathway in IL-6-mediated GC resistance. Although CNTO 328 alone induced minimal cell death, it potentiated dex-mediated apoptosis, as evidenced by increased activation of caspases-8, -9 and -3, Annexin-V staining and DNA fragmentation. The ability of CNTO 328 to sensitize HMCLs to dex-mediated apoptosis was preserved in the presence of human bone marrow stromal cells. Importantly, the increased activity of the combination was also seen in plasma cells from patients with GC-resistant myeloma. Taken together, our data provide a strong rationale for the clinical development of the CNTO 328/dex regimen for patients with myeloma.     

肿瘤坏死因子α、白介素6及白介素8在小儿支气管肺炎中检测的临床意义

目的 探讨血清肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)、白介素6(interleukin-6,IL-6)和IL-8的水平与小儿肺炎的关系.方法 采用放射免疫法对60例支气管肺炎患儿(分为轻型和重型)进行了TNF-α、IL-6和IL-8水平检测,并与30名正常健康儿童作比较.结果 重型肺炎与轻型肺炎患儿血清TNF-α、IL-6和IL-8水平均高于正常对照组(P值均<0.01),重型肺炎患儿血清TNF-α、IL-6和IL-8水平均高于轻型肺炎患儿(P值均<0.01).肺炎患儿血清TNF-α、IL-6和IL-8之间呈显著正相关(P值均<0.001).结论 TNF-α、IL-6和IL-8在小儿肺炎中起重要作用,检测支气管肺炎患儿血清TNF-α、IL-6和IL-8的水平对诊断、治疗和预后均有一定的临床意义.     

白血病患者脑脊液中可溶性白介素—2受体、白介素—6水平的测定及其临床意义

目的　探讨可溶性白介素 2受体 (sIL 2R)、白介素 6 (IL 6 )在急性淋巴细胞性白血病(ALL)的脑脊液 (CSF)中的表达及意义。方法　用双抗夹心ELISA法测定 30例ALL患者CSF中sIL 2R、IL 6水平 ,并与 10名正常者进行对照。结果　ALL合并中枢神经系统白血病 (CNS L)组较CNS L已缓解及未合并CNS L组二者水平显著升高 (P <0 .0 1) ;CNS L已缓解组二者水平接近对照组 (P >0 .0 5 ) ;骨髓缓解及好转组二者水平低于治疗无效组。结论　监测二者水平变化有助于CNS L早期诊断、评估疗效及预后。     

Clinical experience with Sulprim

Sulprim is composed of trimethoprim and sulphametoxazol. By potentiation of a bactericidal effect develops with a very broad antibacterial spectre. The Polish experiences in the therapy of infections of the urinary tracts, infections of the respiratory tract, gonorrhoea, bacterial skin diseases, combustions and paediatric infections confirm the equivalence with foreign preparations of the same composition. All side effects were reversible.     

Interleukin-1-induced interleukin-6 is required for the inhibition of proteoglycan synthesis by interleukin-1 in human articular cartilage

Cartilage from normal controls, patients with osteoarthritis, and patients with rheumatoid arthritis produced no interleukin-6 (IL-6) in culture. However, IL-1 induced massive production of IL-6 (up to 135 ng/ml) in cartilage from all 3 sources, in a dose-dependent manner (in some cases, a peak value was reached). The levels of induced IL-6 were similar to those found in rheumatoid arthritis synovial fluid. At IL-1 concentrations that induced almost complete inhibition of proteoglycan (PG) synthesis, IL-6 production could still be increased considerably. Exogenous IL-6 inhibited PG synthesis by up to 25%. IL-1-induced inhibition of PG synthesis was reversed by antibodies against recombinant human IL-6. These results suggest that IL-6 is required for the IL-1-induced inhibition of PG synthesis.     

Clinical experience with lamivudine

Lamivudine, an oral nucleoside analogue, has demonstrated efficacy against the hepatitis B virus (HBV) in both HBeAg-positive and HBeAg-negative patients with chronic hepatitis B. Treatment with lamivudine is safe and well tolerated and induces a virological and biochemical response in most patients within a short time. Significant histological improvement was seen in clinical trials after 52 weeks of lamivudine treatment. However, durable posttreatment remission of chronic hepatitis B has not been shown to occur in a significant number of lamivudine-treated patients. To maintain the response to treatment, therefore, long-term therapy is required. Prolongation of therapy, however, is associated with the emergence of HBV resistance to lamivudine in most patients. This is accompanied by virological rebound and reversal of the initial therapeutic response, and sometimes by exacerbation of hepatitis. The need remains for effective, safe, and tolerable oral agents with durable activity against HBV.