Serum concentration of IL-2, IL-6, TNF-alpha and their soluble receptors in children on maintenance hemodialysis

In chronic renal failure patients a state of immunodeficiency paradoxically coexists with the activation of immune effector cells, including monocytes and lymphocytes. The activation of these cells leads to the release of cytokines. The aim of this study was to estimate the serum concentrations of IL-2, IL-6, TNF-alpha and their soluble receptors: IL-2 sRalpha, IL-6 sR, sTNF RI in children with chronic renal failure and young adults on maintenance hemodialysis (HD). The study included 16 HD patients (11 females, 5 males) aged 11-22 (mean 16.1 +/- 3.1) years and a control group of 15 age-matched healthy children. Only the mean concentration of IL-6 was similar in HD patients and the control group. The levels of the other cytokines were significantly higher in patients undergoing HD compared to the healthy subjects. No significant differences were observed between the pre- and post-dialysis values or between the values obtained using various dialyzer membranes. These data suggest that immune cells in HD children are in an activated state and that neither a single dialysis session nor the type of dialyzer membrane has an influence on the cytokines examined.     

Lymphocyte release of soluble IL-2 receptors in patients with minimal change nephropathy.

Minimal change nephrotic syndrome has been reported to be a lymphocyte-mediated disorder. It has been suggested that the secretion of lymphokine(s) is involved in the pathogenesis of MCN and in determining proteinuria. The presence of a soluble form of IL-2 receptor (sIL-2R) has been previously described in the sera of patients with some autoimmune disorders. In this work, we report the detection of high sIL-2R levels, both in the plasma (mean value 844 +/- 436 U/ml versus normal value 276 +/- 86 U/ml) and urine of patients with MCN during the nephrotic phase alone. Instead, when the patients achieve stable remission, sIL-2R levels decrease to within normal values (mean value 332 +/- 272 U/ml). Furthermore, during the nephrotic syndrome we observed a significant inverse relationship between sIL-2R plasma levels and the mitogenic response to PHA (p less than 0.005). Since sIL-2R exerts a down-modulation on T-proliferative expansion, sIL-2R might represent one of the inhibitory serum factors extensively reported in the serum of patients with MCN-induced nephrotic syndrome.     

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.     

The cytokines IL-1beta and IL-1 receptor antagonist, IL-2 and IL-2 soluble receptor-alpha, IL-6 and IL-6 soluble receptor, TNF-alpha and TNF soluble receptor I, and IL10 in drained and systemic blood after major orthopaedic surgery.

OBJECTIVE: To measure the concentration of the cytokines interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumour necrosis factor-alpha (TNF-alpha) and the modulators of their function interleukin-1 receptor antagonist (IL-1Ra), interleukin-2 soluble receptor alpha (IL-2 sRalpha), interleukin-6 soluble receptor (IL-6sR) and soluble tumour necrosis factor receptor I (sTNFR-I) in systemic and drained blood for the first six hours after a major orthopaedic operation. DESIGN: Prospective study. SETTING: University hospital, Oslo. PATIENTS: 8 patients operated on for thoracic scoliosis. MAIN OUTCOME MEASURE: Concentrations of IL-1beta, IL-2, IL-6, IL-10, TNF-alpha, IL-1Ra, IL-2 sRalpha , IL-6sR, and sTNFR-I were measured together with haemoglobin (Hb) concentration, white cell count (WCC), and differential count in arterial and drained blood at wound closure and 1, 2, 4, and 6 hours postoperatively. RESULTS: IL-1beta and IL-6 concentrations increased significantly in drained blood, whereas that of TNF-alpha increased only in arterial blood. The modulating factors IL-1Ra, sTNFR-I, and IL-10 were increased both in arterial and drained blood. IL-6sR had decreased slightly at 6 hours in drained blood. No IL-2 was found and IL-2 sRalpha decreased simultaneously with the haemodilution. In arterial blood there was a granulocytosis and in drained blood a relative lymphocytosis. CONCLUSION: Cytokine responses to surgical trauma include modulating factors such as soluble receptors and receptor antagonists that have different responses systemically and locally.     

后腹腔镜CO2气腹对机体免疫功能的影响

目的：探讨后腹腔镜CO2气腹对机体免疫功能的影响。方法：前瞻性研究患者在后腹腔镜CO2气腹手术前后静脉血中IL-2和IL-6值的变化,以了解后腹腔镜CO2气腹对机体免疫功能的影响。以腹膜后开放手术作为对照。结果：腹腔镜组患者术前、手术开始45min、手术后第1天和手术后第3天IL-2值为先下降后回升,但此变化差异无统计学意义（P〉0．05）;IL-6值为先升高后下降,但此变化亦无统计学意义。而开放手术上述4时间段IL-2值为先下降后升高,此变化规律与腹腔镜手术相仿;IL-6值为先升高后下降,此变化规律亦与腹腔镜手术相仿,但上述变化均无统计学意义（P〉0．05）。结论：后腹腔镜CO2气腹对机体免疫功能的影响小,可能与后腹腔镜气腹空间小、对机体尤其是内脏功能干扰小有关。     

氟比洛芬酯对大肠癌患者术后血清IL-2、IL-6的影响

为探讨氟比洛芬酯静脉注射对大肠癌患者术后血清白介素-2（IL-2）、白介素-6（IL-6）的影响,将120例ASAⅠ-Ⅱ级拟行直肠癌根治术的患者随机分为3组,氟比洛芬酯组（F组）、吗啡组（M组）和曲马多组（T组）各40例。3组均以咪达唑仑0．06mg／kg、芬太尼5μg／kg、丙泊酚1.0mg／kg、罗库溴铵1．5mg／kg麻醉诱导后行气管插管,以七氟烷吸入维持麻醉深度（MAC值2．1左右）,术中间断静脉注射顺苯磺酸阿曲库铵维持肌松。于麻醉诱导前10minM组静脉注射吗啡0．1mg／kg,T组静脉注射曲马多1．5mg／kg,F组静脉注射氟比洛芬酯1．5mg／kg。3组分别于术前（T0）、手术结束后3h（T1）、术后1d（T2）和术后3d（T3）取外周静脉血以酶联免疫吸附试验（ELISA）测定血清中IL-2、IL-6的浓度。记录患者术后不良反应,包括恶心、呕吐、皮肤瘙痒等。结果显示,M组IL-2水平在术后3h开始下降（P〈0．05）,术后1d时下降到更低的水平（P〈0．01）,术后3d时略有回升,但仍然低于麻醉前的水平（P〈0．05）;T组IL-2水平在术后3h与麻醉前比较无差异,术后1d后逐渐升高（P〈0．05）,在术后3d恢复到术前水平（P〉0．05）;F组IL-2水平术后3h明显升高,持续至术后1d,与麻醉前比较差异有显著性（P〈0．01）,术后3d后略有下降,但仍高于术前水平（P〈0．05）。3组IL-6血清浓度术后3h全部升高,术后1d达顶峰。T组与F组术后1d血清IL-6浓度与M组相比有统计学差异（P〈0．05）,而F组升高的幅度较T组小（P〈0．01）。术后3d F组与M组血清IL-6浓度相比,仍有显著性差异（P〈0．05）。M组不良反应的发生率显著高于其他两组（P〈0．05）。F组恶心、呕吐的发生率与M组相比有显著性差异（P〈0．05）。结果表明,与吗啡和曲马多相比,氟比洛芬酯可更好地促进IL-2的分泌,抑制IL-6的升高,且术后不良反应发生率更低,围手术期镇痛更为安全有效。     

自体血回输及异体输血前后病人血浆IL-2及IL-6的变化

目的 比较全麻下骨科手术自体血回输及异体输血对病人血浆白介素－2（IL－2）及白介素－6（IL－6）的影响。方法 57例骨科病人,随机分为两组：Ⅰ组,自体血回输,31例：Ⅱ组,异体输血,26例。两组均于麻醉前、术后第2天、第7天采外周静脉血3ml,肝素抗凝离心后取血浆冷冻备检测。结果 术后第2天,Ⅱ组IL－2较术前及Ⅰ组明显下降（P＜0.05）;IL－6在术后第2天、第7天两组病人都有升高;术后第2天Ⅰ组较术前和Ⅱ组升高非常显著（P＜0.01）,术后第7天Ⅰ组升高显著（P＜0.05）。结论 自体血回输组病人IL－2下降不明显,IL－6明显升高,对病人的免疫功能影响较小;异体输血组IL-2明显下降,IL－6升高不显著,对病人的免疫功能有一定的抑制作用。     

Expression of IL-2alpha and IL-2beta receptors on the membrane surface of human sperm

Cytokines are secreted proteins that act as local immunological mediators. Increased seminal cytokine concentrations are associated with fertility problems. The purpose of the present study was to investigate the presence of IL-2alpha, and IL-2beta receptors on fresh and isolated sperm by flow cytometry and transmission electron microscopy. Twenty sperm samples from oligospermic men were incubated with CD25, a mouse monoclonal antibody specific for IL-2alpha-chain receptor, and CD122, a mouse monoclonal antibody specific for IL-2beta-chain receptor. The strong initial fluorescence intensity and, subsequently, a labeling index yielded by CD25 and CD122 decreased in sperm centrifuged on a Percoll gradient (p < .05). The expression of CD25 and CD122 correlated negatively with fresh sperm concentration, but in sperm centrifuged on a Percoll gradient there was no correlation. Labeling with CD25 and CD122 antibody was evident on the head and the middle piece in fresh sperm, while in sperm centrifuged on a Percoll gradient a weak labeling was observed only on the principal piece. The authors have identified and localized cytokine receptors on human sperm for the first time. Cytokine receptors may be involved in the regulation of pathophysiological events in sperm cell functions and male infertility. The exact pathway involved in modulation of these receptors requires further investigation. These results contribute to the understanding of cytokine-sperm relationships.     

Analysis of IL-6, IL-10 and IL-17 genetic polymorphisms as risk factors for sepsis development in burned patients

Infection risk, sepsis and mortality after severe burn are primarily determined by patient age, burn size, and depth. Whether genetic differences contribute to otherwise unexpected variability in outcomes is unknown. We sought to determine whether there was an association between IL-6, IL-10 and IL-17 polymorphisms with cytokine production and development of sepsis. We evaluated 71 patients with burns ≥15% TBSA and 109 healthy subjects. The genotypes of IL-6 (-174C/G), IL-10 (-819C/T and -1082A/G) and IL-17 (7488T/C) polymorphisms were identified applying polymerase chain reaction protocols. The cytokine levels in serum were determined with enzyme-linked immunoabsorbent assays. Our results demonstrated no significant differences in the genotype frequencies studied between burn patients and healthy subjects. No significant associations were found among IL-6 and IL-17F genotypes and the related cytokine serum levels. Only IL-10 promoter -1082GG genotype was related to an increased IL-10 production in burned patients. In addition, septic subjects bearing -1082G/G genotype have shown the highest and non-septic bearing -1082A/* genotypes the lowest IL-10 serum levels. All together these data seem to indicate that genetically determined individual difference in IL-10 production might influence the susceptibility to septic complications in burned patients and suggest that these markers might be useful in burned patient management.     

Hormonal changes in haemodialysed and in kidney-transplanted patients

A total of 48 haemodialysed patients were studied by radioimmunoassay for the serum concentrations of parathormone, calcitonin, gastrin, insulin, prolactin, T₃, T₄, rT₃, TSH and cortisol. Residual urines were measured for cAMP and ultrafiltrates for iPTH and gastrin. The duration of the dialysis programme, the number of haemodialysis sessions per week, sex distribution, the dialysis alternatives (including haemofiltration, haemoperfusion) and successful kidney transplantations were correlated with the serum hormone levels. Significant increases in PTH gastrin and prolactin values were demonstrated in the dialysed patients. However, their calcitonin and insulin concentrations decreased, parallel with the time elapsed since the start of the haemodialysis programme (HDP). The number of dialysis sessions per week was found to affect the hormone concentrations diversely. In the course of hemofiltration and haemoperfusion some of the centrations diversely. In the course of haemofiltration and haemoperfusion some of the hormone levels (e.g. PTH, gastrin) decreased significantly. The patients were in general euthyroid. One of them, on HDP for several years, developed clinical and laboratory signs indicative of hyperthyroidism. In a considerable proportion of the cases the results of the hormone studies (increased PTH, CT, cAMP) were consistent with secondary hyperparathyroidism. Kidney transplantation was followed by a decline of the serum prolactin, parathormone, calcitonin and aldosterone levels.     

罗比卡因-芬太尼术后镇痛对乳腺癌患者患者白细胞介素-2和白细胞介素-6的影响

目的探讨罗比卡因复合芬太尼行硬膜外自控镇痛(PCEA)对乳腺癌患者术后白细胞介素-2(IL-2)和白细胞介素-6(IL-6)的影响。方法40例乳腺癌根治术患者随机分为两组,每组20例。Ⅰ组为罗比卡因复合芬太尼组;Ⅱ组为罗比卡因复合吗啡组。分别于麻醉前(T0)、术后2h(T1)、24h(T2)、72h(T3)采集外周静脉血,测定T淋巴细胞亚群及IL-2、IL-6水平。结果两组镇痛效果良好,与麻醉前比较,Ⅰ组T淋巴细胞亚群及IL-2水平各时点之间无显著性差异(P>0·05);与Ⅰ组比较,Ⅱ组T1、T2时的CD3+、CD4+、IL-2均明显下降(P<0·05)。结论罗比卡因复合芬太尼行PCEA效果良好,对免疫的抑制作用较轻,适合乳腺癌患者术后镇痛。     

腹腔镜和开腹胆囊切除术对患者血清细胞因子IL-6、IL-10和IL-18的影响

目的:探讨腹腔镜胆囊切除术(LC)和开腹胆囊切除术(OC)对慢性结石性胆囊炎患者血清IL-6、IL-10和IL-18影响,比较两种方法对机体肝功能的损伤和机制。方法:选择LC患者和OC患者各30例,分别于术前、术后1d、5d抽取静脉血测定血清ALT、AST、IL-6、IL-10和IL-18含量,并进行对比研究。结果:LC组和OC组术后血清ALT、AST、IL-6和IL-18含量均较术前增加(P<0.01),血清IL-10含量较术前降低(P<0.01),上述指标术后1d变化最为明显,LC组上述血清指标变化小于同期OC组(P<0.05)。结论:LC对患者肝功能损伤较OC小,可能与LC刺激机体产生IL-6和IL-18较少,维持较高血清IL-10水平,维护适度机体细胞因子平衡有关。     

Effect of heparin and prostacyclin-heparin infusion on blood coagulation in haemodialysed patients

In 10 patients (8 men and 2 women) aged 28 to 58 years (mean 44.4 years) treated by repeated haemodialysis due to end-stage renal failure, the bleeding time, whole-blood coagulation time, one-stage prothrombin time, thrombin time of plasma, activated partial thromboplastin time (APTT), fibrinogen level and euglobulin lysis time have been determined (1) during a 4-hour haemodialysis using heparin as an antithrombotic agent, and (2) one week later in the course of another haemodialysis using prostacyclin-heparin. The values for any of the above parameters with both anticoagulant treatment types did not differ. Plasma fibrinogen level after haemodialysis was significantly lower after administration of heparin alone as compared with the group treated by prostacyclin-heparin infusion. During haemodialysis performed with prostacyclin-heparin infusion, activation of the blood fibrinolytic system was manifested by a significant shortening of euglobulin lysis time, observed after 1.5 hours and after the end of haemodialysis. The above phenomenon did not occur when haemodialysis was performed with heparin alone.     

Hearing loss in short- and long-term haemodialysed patients

BACKGROUND.: Hearing loss has been described in patients with chronic renalfailure on regular dialysis treatment (RDT) with very differentfrequency, ranging from 20 to 75%; RDT does not seem to worsenhearing function for at least the first 5 years of treatment;no studies are available on patients on RDT for more than 10years. METHODS.: We performed an audiometric evaluation in 91 patients on RDTfor various periods: group I (34 patients), <5 years; groupII (32 patients), 5–10 years; group III (25 patients),> 10 years; patients with histories of chronic otitis, ototoxicdrug treatment, and chronic auditory trauma were excluded; thepossible correlations with some biochemical parameters (urea,creatinine, PTH) were also looked for. RESULTS.: Hearing loss was present in 77% of patients and 69.2% of ears;the percentage of patients with hypoacusia was higher in groupIII (84%) than in group I (76.3%) and II (71.7%), but the differenceswere not statistically significant. Hypoacusia was cochlearneurosensory in 61.5%, conductive in 6.5%, and mixed in 9.0%of patients; the percentage of patients with cochlear neurosensoryhypoacousia was similar in the three groups (I, 61.7%; II, 59.3%;III, 64%). Hearing loss was of slight to moderate degree andnot different in the three groups (I, 22.7±15 dB; II,26.9±6.0 dB; III, 29.1±8.9 dB). There were nocorrelations between hearing loss and plasma creatinine andPTH values; patients with plasma urea >200 mg/dl had higherpercentage of hypoacousia (86%) than patients with plasma urea<200 mg/dl (69%) (P=0.06). CONCLUSIONS.: Hearing loss, mainly cochlear neurosensory in type, is presentin a high percentage of patients on RDT even at the beginningof treatment, but no negative effects on hearing can be correlatedwith the duration of dialysis.     

中药狼疮方对狼疮样小鼠外周血IL-6和IL-10水平的影响

目的 :探讨狼疮样小鼠外周血IL - 6和IL - 10水平及中药狼疮方对其影响。方法 :采用慢性移植物抗宿主病小鼠模型 ,经中药狼疮方、强的松及联合治疗后分别检测血清抗ds -DNA抗体、和IL - 6、IL - 10水平。结果 :( 1)模型组血清抗ds -DNA抗体为 1.75± 0 .2 5 ,与对照组比较差异显著 ( 1.2 0± 0 .2 1,P <0 0 0 1) ;各治疗组血清抗ds-DNA抗体与对照组比较差异不显著 (P >0 0 5 )。 ( 2 )模型组狼疮样小鼠血清Th2 细胞因子IL - 6和IL - 10水平明显高于对照组及各治疗组 ,差异显著 (P <0 0 5 )。结论 :狼疮方具有免疫抑制作用 ,可抑制T和B细胞活化、减少Th2细胞因子的形成、自身抗体产生 ,有效的治疗狼疮性肾炎。     

Effect of dialysis membranes on lipoprotein profile of serum in haemodialysed patients

The subjects of the studies were 31 haemodialysed (HD) patients with chronic renal insufficiency (CRI). In this group of patients the lipoprotein profile was determined and 8 patients were selected for further studies. During the study the patients were treated with cuprophane membranes for 6 months. For the next 6 months the same patients were treated using polysulfone dialysers, and for further 6 months HD with polysulfone dialysers was continued. Patients' sera were tested after every 6 months of treatment. The Δ values were calculated as 6-month HD with polysulfone minus 6-month HD with cuprophane (ΔI) and 12-month HD with polysulfone minus 6-month HD with polysulfone (ΔII). We concluded that after long-term HD with low flux polysulfone treatment the lipoprotein profiles improved, but the mechanism of the process is not clear.