Correlation of serum IL-2, IL-6 and IL-10 levels with International Prognostic Index in patients with aggressive non-Hodgkin's lymphoma

Cytokines play important roles in the pathogenesis of lymphomas. The aim of this study was to determine the relations between serum levels of interleukin-2 (IL-2), IL-6, and IL-10 and parameters of International Prognostic Index (IPI). Serum levels of IL-2, IL-6, and IL-10 were measured using a sensitive enzyme-linked immunosorbent assay in the pretreatment frozen sera from 43 patients with non-Hodgkin's lymphoma. The patients we included in the study were divided into two groups, one with high risk and the other with low risk according to the IPI in regard to their ages, stages, performance status, extranodal involvements, and serum levels of lactate dehydrogenase. In the high-risk group, serum levels of IL-2 (0.852 +/- 0.268 ng/ml), IL-6 (0.461 +/- 0.206 ng/ml), and IL-10 (0.816 +/- 0.240 ng/ml) were found to be higher than serum levels of IL-2 (0.667 +/- 0.170 ng/ml), IL-6 (0.355 +/- 0.075 ng/ml), and IL-10 (0.643+0.177 ng/ml) in the low-risk group ( < 0.05). There was a correlation between the patients with high risk according to the IPI criteria and high levels of serum cytokines (IL-2, IL-6, IL-10). Knowledge of the serum levels of these cytokines in patients with newly diagnosed aggressive non-Hodgkin's lymphoma may help us to have some information about the possible prognosis, the activation of disease, and to decide on appropriate therapeutic approaches for individual patients.     

Correlation and prognostic value of serum soluble ICAM-1, beta-2 microglobulin, and IL-2alphaR levels in non-Hodgkin's lymphoma.

Serum levels of sICAM-1, sIL-2alphaR, and beta-2 microglobulin were measured in 63 patients with non-Hodgkin's lymphoma (NHL). The correlation between these serum markers as well as their relationship with NHL features and disease outcome were analyzed. Although in high-grade NHL sICAM-1 levels correlated with tumor mass, no correlation was found between sICAM-1 levels and tumor burden in low-grade NHL. When compared with sICAM-1 and beta-2 microglobulin, sIL-2alphaR showed the strongest correlation with the tumor burden. However, in multivariate analysis, including serum markers employed as continuous variables, the only parameteres which entered the regression model were beta-2 microglobulin (p=0.012) and sICAM-1 (p=0.019). In a dichotomized model, beta-2 microglobulin, aggressive histology, sICAM-1, age and number of nodal involved sites were found to be prognostically significant. Finally, by combining sICAM-1 and beta-2 microglobulin serum levels, a simple prognostic model useful for NHL was obtained.     

癌性渗出液中IL-2、IL-6、IL-8、TNFα·论著·和IFNγ活性分析

目的与方法应用ＥＬＩＳＡ法研究了１８例癌性渗出液（ＭＯＦ）中内源性ＩＬ－２、ＩＬ－６、ＩＬ－８、ＩＦＮγ和ＴＦＮα的生物学活性,并与恶性肿瘤病人（ＭＴＤ）血清、正常人、结核性胸膜炎（ＴＢＰ）和肝硬化病人（ＣＲＳ）进行了比较分析。结果ＭＴＤ血清中ＩＬ－６活性高于与正常成人组（Ｐ＜０．０５）;ＩＬ－２和ＩＦＮγ活性亦低下（Ｐ＜０．５）。ＭＴＤ血清中ＩＬ－２、ＩＬ－６ＴＮＦα活性显著低于ＴＢＰ（Ｐ＜０．００１）;ＩＬ－８和ＩＦＮγ活性亦降低（Ｐ＜０．０５）。ＭＯＦ中的ＩＬ－６、ＩＦＮγ水平显著高于ＴＢＰ组（Ｐ＜０．０１;Ｐ＜０．０５）;ＩＬ－２却明显降低（Ｐ＜０．０５）。ＭＴＤ血清中ＩＬ－２、ＩＬ－６低于ＣＲＳ组（Ｐ＜０．０５）;ＭＯＦ中ＩＬ－６、ＩＮＦγ水平高于ＣＨＡＤ组（Ｐ＜０．００１;Ｐ＜０．０５）;ＩＬ－２和ＩＬ－８则低于ＣＲＳ组（Ｐ＜０．０５;Ｐ＜０．０１）。结论ＭＴＤ血清和ＭＯＦ中ＩＬ－２、ＩＬ－６、ＩＬ－８和ＩＦＮγ活性反映了ＭＴＤ抗肿瘤免疫的功能状态。ＩＬ－６和ＩＬ－８活性对于ＭＴＤ预后的估计具有重要的意义。     

Correlation of serum metalloproteinase levels with lung cancer metastasis and response to therapy.

Cancer cells elaborate metalloproteinases which may play a role in invasion and metastasis. The serum level of the M(r) 72,000 type IV collagenase (MMP-2) was measured in 87 lung cancer patients. Stage IV cancer levels were significantly elevated (P less than 0.0001) compared to normal sera. A significant difference (P less than 0.01) was found between enzyme levels in the presence versus the absence of distant metastasis. For 29 patients treated with combination chemotherapy, a positive relationship was noted between response failure and elevated enzyme levels. Serum metalloproteinase levels may provide information relevant to prognosis as well as treatment decisions.     

Soluble interleukin-2 receptor serum levels in mycosis fungoides. Correlation with clinical stage.

BACKGROUND. In a variety of non-Hodgkin lymphomas, a correlation between soluble interleukin-2 receptor levels (sIL-2R) and clinical stage is demonstrable. In mycosis fungoides (MF), two findings raise the question as to a similar correlation: (1) a proportion of tumor cells express IL-2 receptor and (2) sIL-2R is detectable in serum. METHODS. sIL-2R were measured in patients with MF (n = 88) and atopic dermatitis (AD) (n = 14) by the enzyme immunoassay technique. Patients with AD served as controls. Cases of MF were classified according to the TNM staging classification. RESULTS. Sera of patients with MF with stages III, IVa, and IVb showed significantly higher values than those of stage I or II and controls. CONCLUSIONS. Although a close and significant correlation was found between sIL-2R levels and stage of disease in MF, it is still not clear whether elevated sIL-2R levels reflect disease activity or T-cell activation due to concomitant immunologic processes.     

Association of IL-1 polymorphisms and IL-1 serum levels with susceptibility to nasopharyngeal carcinoma

Previous studies demonstrated that the polymorphism of interleukin-1 (IL-1) produce alterations of the protein expression and may contribute to oncogenetic processes. The aim of this study was to investigate the relationship between IL-1A gene polymorphisms and NPC susceptibility and the influence of on IL-1α serum levels in cases versus controls. To test whether the genetic variants of IL-1A gene modify the risk of nasopharyngeal carcinoma (NPC), we compared the -889C/T and rs3783553 polymorphisms between 248 patients with NPC and 296 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Serum IL-1α levels were measured by enzyme-linked immunosorbent assay. The rs3783553 (TTCA insertion or deletion) polymorphism of the IL-1A gene was significantly associated with the susceptibility to NPC. The variant homozygote genotype +/+ was associated with a significantly reduced risk of NPC as compared with the wild homozygote -/- genotype, and the serum IL-1α levels were significantly lower in individuals with homozygous +/+ genotypes. No association was found between the -889C/T polymorphisms and risk of NPC, and no statistically significant differences were found between rs3783553 polymorphism and clinical pathology indices. The IL-1A rs3783553 polymorphism might contribute to a risk of developing NPC by affecting the serum IL-1α secretion in the Chinese population.     

鼻咽癌患者血浆EB病毒DNA水平的动态变化与临床疗效的关系

背景与目的：鼻咽癌是一种与EB病毒相关的肿瘤。最近,一些学者报道了鼻咽癌患者血浆或血清中可检测到EB病毒DNA,本研究观察晚期鼻咽癌患者同期放化疗中血浆EB病毒DNA水平的动态变化以及与临床疗效的关系。方法：20例初治患者在同期放化疗期间每周抽血一次,共7次,每一次抽血时间为治疗前,所有的标本均采用荧光定量PCR的方法,在PE7700型检测仪上定量检测血浆标本中EB病毒DNA的含量。结果：90%（18/20）患者治疗前的血浆中可检测到EB病毒DNA,中位浓度为150000copies/ml,2例患者自治疗开始至结束血浆中均未检测到EB病毒DNA,18例阳性患者中,3例患者在治疗期间可检测到持续高水平的EB病毒DNA,治疗后临床结果显示三者均有肿瘤残留,7例患者EB病毒DNA水平在治疗开始后迅速下降至检测不到;8例患者血浆EB病毒DNA水平下降缓慢,但在治疗结束时,EB病毒DNA均检测不到。临床结果显示,此15例患者均达到完全缓解。结论：血浆EB病毒DNA水平的变化与鼻咽癌患者临床疗效关系密切,值得进一步研究。     

Serum levels of IL-1 beta, sIL-2R, IL-6, IL-8, and TNF-alpha in febrile children with cancer and neutropenia

Serum levels of interleukin-1 beta (IL-1beta), soluble interleukin 2 receptors (sIL-2R), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) were measured to predict some characteristics of febrile episodes in children with cancer and neutropenia. Forty-eight episodes of febrile neutropenia were determined in 23 pediatric cancer patients, including 35 febrile episodes without identifiable source, 7 episodes of bacteremia due to Gram-negative organisms and 4 due to Gram-positive organisms, and 2 fungal infections. Interleukin-6, sIL-2R, and IL-8 levels were significantly higher at the beginning of the febrile episodes than those of controls (p < 0.001, p < 0.001, and p < 0.001). Interleukin-6, slL-2R, and IL-8 levels were higher in patients with bacteremia due to Gram-negative organisms than in those with Gram-positive ones (p = 0.042, p = 0.006, and p = 0.023, respectively). TNF-alpha and IL-1beta levels were similar in febrile episodes and controls (p > 0.05). In conclusion, sIL-2R, IL-6, and IL-8 levels may be helpful in the prediction of infection in febrile cancer patients with neutropenia and measurements of IL-1beta and TNF-alpha were not useful for identifying the presence and the type of infection in febrile neutropenic episodes in children.     

平消胶囊治疗良性甲状腺结节的临床疗效及对血清IL-1β与IL-6水平的影响北大核心

目的:探讨平消胶囊治疗良性甲状腺结节的临床疗效及其作用与血清白细胞介素-1β(interleukin-1β,IL-1β)与白细胞介素-6(interleukin-6,IL-6)水平的关系。方法:选取经细针穿刺细胞学病理为良性的100例甲状腺结节患者作为研究对象,随机分为治疗组与观察组各50例,同时招募甲状腺B超正常的健康人50例作为对照组。三组随访期间均食用无碘盐,忌海产品等富碘食物,治疗组加用平消胶囊,时间为6个月。比较治疗前后观察组与治疗组结节的大小和甲状腺相关激素水平;比较对照组、治疗组治疗前后血清IL-1β、IL-6的水平。结果:治疗后,观察组的结节直径较治疗前无统计学差异,治疗组的结节直径较治疗前减小(P<0.05)。观察组的有效率为12%,治疗组的有效率为70%,治疗组有效率高于观察组(P<0.05)。治疗后,观察组与治疗组的甲状腺相关激素的水平较治疗前无统计学差异(P>0.05)。治疗组患者的IL-1β水平高于对照组(P<0.05),IL-6水平低于对照组(P<0.05);治疗后,治疗组IL-1β和IL-6水平较治疗前提高(P<0.05);治疗后,治疗组IL-6水平与对照组相比无统计学差异(P>0.05)。结论:平消胶囊能减小良性甲状腺结节的直径,可能与调节IL-1β、IL-6的水平相关。     

High serum levels of TNF-α and IL-6 predict the clinical outcome of treatment with human recombinant erythropoietin in anaemic cancer patients

BackgroundA number of anaemic cancer patients are not responsive to treatment with recombinant human erythropoietin (rHuEPO). The aim of the present study is to investigate whether serum levels of tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-6 and additional laboratory parameters, together with clinical variables, can predict the clinical outcome of treatment with rHuEPO in anaemic cancer patients.Patients and methodsThirty-five cancer patients and 25 healthy controls were enrolled in this study. Patients were treated with epoetin alfa at the dose of 150 IU/kg s.c. three times a week for 12 weeks. If the haemoglobin (Hb) level failed to improve at least 2 g/dl above baseline by week 6 of treatment, dose was increased to 300 IU/kg s.c. for the remainder of the treatment period. All patients filled out the Brief Fatigue Inventory (BFI), a questionnaire for the self-evaluation of cancer-related fatigue. Serum samples from patients and control groups were frozen at -80°C and TNF-α, IL-1β and IL-6 were later examined by enzyme-linked immunosorbent assay.ResultsFatigued cancer patients had significant higher levels of circulating TNF-α, IL-1β and IL-6 than healthy controls. Responders (Rs) to erythropoietin had significant lower medium levels of TNF-α and IL-6 than nonresponders (NRs). Fatigued patients with a general BFI score ≥6 presented higher medium level of cytokines than nonfatigued patients (general BFI score <6), but each group responded similarly to treatment with rHuEPO.ConclusionsHigh serum levels of TNF-α and IL-6 at the baseline are significantly correlated with a negative response to administration with rHuEPO. Thus, pretreatment evaluation of TNF-α and IL-6 serum levels can help to select those patients who are most likely to benefit from treatment with rHuEPO. On the contrary, Hb level, red blood cell count, lactate dehydrogenase and BFI score do not predict the outcome of treatment with rHuEPO.     

Basic and clinical aspects of IL-6]

Interleukin-6 (IL-6) is a pleiotropic cytokine regulating immune response, production of acute phase reactants in hepatocytes, growth of hematopoietic stem cells and other cellular functions in many cell lineages. The increased production of IL-6 is often seen in infections diseases, chronic inflammatory diseases, and certain tumors which accompany polyclonal B cell activation and increased level of CRP. Recent progress in the study of the basic aspects on IL-6 will be discussed, which includes the regulation mechanisms of IL-6 gene, the structure of IL-6 receptor complex (IL-6, 80 KDa IL-6 receptor and signal transducing gp130) and IL-6 signal transduction pathways.     

IL-6, M-CSF and IAP cytokines in ovarian cancer: simultaneous assessment of serum levels.

The aim of this study was to simultaneously determine IL-6, M-CSF and IAP levels in 61 serum samples of previously untreated ovarian cancer patients. A direct correlation between IL-6 and M-CSF has been found in our patient population (r = +0.41, p = 0.013), while IAP serum levels failed to correlate with M-CSF (r = +0.15, p = 0. 24) and IL-6 (r = +0.17, p = 0.18) levels. Since IL-6 and M-CSF have been demonstrated to be both induced in response to the same agents, it is conceivable that a mechanism of coregulation in the production of these cytokines by tumor cells and macrophages might occur. The direct correlation between IL-6 and M-CSF also suggests that tumor-derived cytokines can potentially lead to a self-maintaining cytokine network by recruiting cytokine-producing host cells and by perpetuating cytokine production.     

血清IL-6及IL-10在非霍奇金淋巴瘤患者血清中的表达及临床意义

目的:探讨细胞白介素-6(IL-6)和白介素-10(IL-10)在非霍奇金淋巴瘤(non-Hodgkin's lym-phoma,NHL)患者中的表达水平及其与患者临床特征、预后的关系.方法:收集我院2013年06月至2016年06月初治的NHL患者278例,回顾性分析IL-6和IL-10的水平.结果:NHL患者外周血...     

Intravenous administration of amphotericin B entrapped in liposomes: induction of high serum levels of TNF alpha.

The rate of objective response to second-line chemotherapy with cyclophosphamide, adriamycin and vincristine increased from 13% to 55% in two consecutive series of patients with small-cell lung cancer when the therapy was potentiated by amphotericin B (2 mg/kg i.v.) entrapped in liposomes (= ampholiposomes). Patients who received ampholiposomes had a rapid and significant (p less than 0.01) increase of serum TNF alpha concentrations (median value: from less than 10 to 261 pg/mL) followed by a rise in serum neopterin and CRP. No major side effects were observed. Administration of ampholiposomes appeared to be a safe method for obtaining relatively high serum levels of TNF alpha that could potentiate anticancer chemotherapy.     

血清白细胞介素2检测在恶性腹水白细胞介素2治疗中的应用

目的 对恶性腹水患者血清白细胞介素2(IL-2)水平进行测定,了解血清IL-2水平与腹腔灌注IL-2治疗疗效之间的关系,以期获得判定恶性腹水IL-2治疗疗效的指标。方法 54例恶性非肝癌性腹水患者均接受IL-2腹腔灌注治疗,治疗前应用ELISA法检测血清IL-2水平,将IL-2测定值较高的27例患者分为A组,IL-2测定值较低的27例患者分为B组。比较两组患者的治疗效果。结果 血清IL-2测定值较低组IL-2腹腔灌注治疗的有效率为77.8％(21/27),明显高于IL-2测定值较高组的51.9％(14/27,P<0.05)。结论 恶性腹水患者IL-2腹腔灌注治疗前血清IL-2水平高低与IL-2治疗的疗效明显相关,原有IL-2水平较低的患者IL-2腹腔灌注治疗的疗效较好。血清IL-2水平可作为判定IL-2腹腔灌注治疗疗效的指标。     

Dynamic changes of specific T cell responses to melanoma correlate with IL-2 administration

Interleukin 2 (IL-2) is a promising immunotherapeutic agent for the treatment of metastatic melanoma and renal cell carcinoma. Systemic administration of high dose IL-2 produces objective responses in up to 25% of melanoma patients, and a low but significant proportion of these patients experience durable responses. Nevertheless, the cells and molecules responsible for induction of tumor regression over the course of IL-2 treatment remain unknown. New strategies in tumor immunotherapy have evolved over the past decade as a consequence of significant progress in the field, in particular with respect to the characterization of peptide epitopes derived from tumor associated antigens, and the role of antigen presenting cells in the initiation of cellular immune responses. Alongside with these factual as well as conceptual advances, new methods have been developed to monitor and characterize anti-tumor T cell responses in cancer patients. Application of these tools to dissect anti-tumor responses has demonstrated that various immune therapeutic approaches can induce powerful systemic anti-tumor cytotoxic T lymphocyte (CTL) responses. However, only limited efforts have been made to use present days tool to analyze anti-tumor immune responses in patients treated with IL-2 based immunotherapy. We have examined CTL responses against known tumor antigens in melanoma patients over the course of IL-2 based immunotherapy (electrochemotherapy). Surprisingly, anti-tumor CTL responses significantly declined upon initiation of therapy, but reappeared when IL-2 administration was paused. Molecular analyses of the clonotypic composition of responding T cells demonstrated that new clones emerged over the course of treatment, and that tumor-specific T cells that had left the peripheral blood could subsequently be detected at the tumor site. These data provide new insight into the biological actions of IL-2 and highlight the difficulties associated with the monitoring of anti-tumor immune responses. This underlines the importance of frequent sampling of blood and tumor biopsies to be analyzed with a combination of state of the art technologies in order to gain detailed information on the interactions between cancer cells and cells of the immune system.     

Changes in serum interleukin-8 (IL-8) levels reflect and predict response to anti-PD-1 treatment in melanoma and non-small-cell lung cancer patients

BackgroundSurrogate biomarkers of efficacy are needed for anti-PD1/PD-L1 therapy, given the existence of delayed responses and pseudo-progressions. We evaluated changes in serum IL-8 levels as a biomarker of response to anti-PD-1 blockade in melanoma and non-small-cell lung cancer (NSCLC) patients.Patients and methodsMetastatic melanoma and NSCLC patients treated with nivolumab or pembrolizumab alone or nivolumab plus ipilimumab were studied. Serum was collected at baseline; at 2–4 weeks after the first dose; and at the time-points of response evaluation. Serum IL-8 levels were determined by sandwich ELISA. Changes in serum IL-8 levels were compared with the Wilcoxon test and their strength of association with response was assessed with the Mann–Whitney test. Accuracy of changes in IL-8 levels to predict response was estimated using receiver operation characteristics curves.ResultsTwenty-nine melanoma patients treated with nivolumab or pembrolizumab were studied. In responding patients, serum IL-8 levels significantly decreased between baseline and best response (P <0.001), and significantly increased upon progression (P =  0.004). In non-responders, IL-8 levels significantly increased between baseline and progression (P =  0.013). Early changes in serum IL-8 levels (2–4 weeks after treatment initiation) were strongly associated with response (P <0.001). These observations were validated in 19 NSCLC patients treated with nivolumab or pembrolizumab (P =  0.001), and in 15 melanoma patients treated with nivolumab plus ipilimumab (P <0.001). Early decreases in serum IL-8 levels were associated with longer overall survival in melanoma (P =  0.001) and NSCLC (P =  0.015) patients. Serum IL-8 levels also correctly reflected true response in three cancer patients presenting pseudoprogression.ConclusionsChanges in serum IL-8 levels could be used to monitor and predict clinical benefit from immune checkpoint blockade in melanoma and NSCLC patients.     

结直肠癌患者术前检测血清血管内皮生长因子白细胞介素6及C反应蛋白的临床意义

目的 探讨结直肠癌患者术前血清血管内皮生长因子(VEGF)、白细胞介素6(IL-6)和C反应蛋白(CRP)水平与临床病理的关系及其对预后的临床意义.方法 采用酶联免疫吸附法检测79例结直肠癌患者血清VEGF和IL-6,采用免疫比浊法检测血清CRP,比较结直肠癌患者与健康对照者的血清VEGF、IL-6和CRP水平.采用Kaplan-Meier法分析结直肠癌患者5年生存率,采用Log rank 单因素分析预后不良因素.结果 结直肠癌组血清VEGF、IL-6和CRp分别为(591±312)pg/ml、(13.2±3.7)pg/ml和(1.14±0.87)mg/dl,健康对照组分别为(321±210)pg/ml、(5.4±2.0)pg/ml和(0.39±0.35)mg/dl,其中VEGF和CRP间差异有统计学意义(P＜0.001,P=0.002).男性患者和女性患者的VEGF水平分别为(638±387)pg/ml和(552±271)pg/ml,差异有统计学意义(P=0.042);肿瘤＜5 cm和肿瘤≥5 cm患者的VEGF表达分别为(538±275)pg/ml和(647±331)pg/ml,差异有统计学意义(P=0.009).男性患者和女性患者的IL-6表达分别为(11.7±3.2)pg/ml和(15.2±4.0)pg/ml,差异有统计学意义(P=0.011).VEGF＜591 pg/ml和≥591 pg/ml患者的5年生存率分别为86.8%(33/38)和73.2%(30/41),IL-6＜13.2 pg/ml和≥13.2 pg/ml患者的5年生存率分别为82.9%(34/41)和76.3%(29/38),CRP＜1.14 mg/dl和≥1.14 mg/dl的5年生存率分别为81.4%(35/43)和77.8%(28/36).Log rank单因素分析显示,VEGF水平是影响结直肠癌预后的相关因素(P＜0.05).Logistic回归分析显示,肿瘤大小和VEGF水平为结直肠癌患者预后的危险因素(P=0.032,OR=0.985;P=0.011,OR=0.976).结论 血清VEGF和IL-6表达具有性别差异,血清VEGF检测可作为结直肠癌患者的临床诊断标志之一,对患者的预后具有重要的临床意义.