血小板减少症患者促血小板生成素和血清白细胞介素-11水平的检测

 目的 探讨血小板减少症患者血清促血小板生成素（TPO）和白细胞介素－11（IL-11）水平及其与外周血小板计数之间的关系。方法 应用双抗体夹心酶联免疫吸附法（ELISA）测定110例 血小板减少症患者血清TPO和IL-11水平,同时用自动血细胞仪测定其血小板数,以20例健康人为正常对照。结果 原发性血小板减少性紫癜（ITP）血清TPO水平较正常对照组低（P＜0.05）,而IL-11水平较对照组高（P＜0.05）;继发性血小板减少症血清TPO明显高于正常对照组（P＜0.05）;再生障碍性贫血患者的IL-11水平较对照组低（P＜0.05）。相关性分析表明, ITP患者血清TPO水平与血小板计数无相关性（r = 0.160,P＞0.05）,继发性血小板减少症患者血清TPO水平与血小板计数呈负相关（r = - 0.820,P＜0.05）;ITP 患者血清IL-11水平与血小板计数呈负相关（r = -0.559,P＜0.05）。继发性血小板减少症患者血清IL-11水平与血小板计数相关性不明显（r = 0.432,P＞0.05）。结论 本实验结果为进一步探讨血小板减少症患者TPO及IL-11的调控机制,为临床诊断、治疗血小板减少症提供新的理论依据。     

基因重组人白细胞介素-11治疗化疗所致血小板减少症临床研究

目的：观察基因重组人白细胞介素-11治疗化疗所至血小板减少症的疗效和不良反应。方法：采用自身对照研究,21例接受GP或GC方案化疗的非小细胞肺癌患者,接受化疗后,当血小板下降至≤50×10^9／L时,治疗周期给予rhIL-11 50μg·kg^-1·d-1,皮下注射,连续用药,当血小板≥100×10^9／L,停药;对照周期单纯用化疗,两个周期化疗结束后评价疗效。结果：治疗周期血小板最低值为（30．58±10．10）×10^9／L,对照周期为（20．36±9．21）109／L（P〈0．005）;血小板恢复至100×10^9／L的时间,治疗周期为3．34天±2．61天,对照周期为5．19天±2．34天（P〈0．005）。治疗周期没有患者出现出血倾向,没有输注血小板,对照周期有6例出现全身皮肤散在出血点,6例输注血小板。不良反应主要是轻度水肿、乏力及感冒样症状等。结论：基因重组人白细胞介素-11治疗化疗所至的血小板减少症疗效确切,不良反应轻,安全。     

重组人白细胞介素-11治疗化疗所致血小板减少的临床观察

目的观察重组人白细胞介素-11(rhIL-11)治疗化疗所致血小板(PLT)减少的疗效和不良反应。方法采用病例自身对照研究,对第1个周期化疗(对照组)后PLT≤70×109／L的32例实体瘤患者,第2个周期(治疗组)采用相同方案化疗,化疗结束后24 h开始,皮下注射rhIL-11 25μg／kg体重,每天1次,连用7～14 d,或至PLT≥100×109／L时停药。结果治疗组化疗后各时点PLT计数均高于对照组。化疗后,治疗组和对照组PLT最低值分别为(110．2±53．5)×109/L和(55．6±46．8)×109／L,两组差异有统计学意义(P<0．01)。PLT恢复正常时间,治疗组为2～18 d,对照组为5-27 d,中位数分别为5 d和12 d,两组差异有统计学意义(P<0．01)。治疗组中PLT输注2例,次数为2次,对照组为7例9次,差异有统计学意义(P<0．01)。乏力、关节肌肉酸痛、注射部位疼痛、头痛、心悸、水肿和发热等不良反应多为Ⅰ度和Ⅱ度,可自行缓解。Ⅲ度不良反应为乏力、关节肌肉酸痛、头痛,对症处理后可缓解。结论rhIL-11是治疗化疗后PLT减少的有效药物,不良反应可以耐受。     

重组人白细胞介素-11治疗化疗后血小板减少的临床研究

目的探讨重组人白细胞介素-11(rhIL-11)治疗化疗后血小板减少症的疗效和用药方法。方法回顾性分析该科2000年2月至2004年9月共38例化疗后出现Ⅲ～Ⅳ度血小板减少患者的治疗效果。对照组18例,用利血生、升血小板胶囊等药物;治疗组20例,用rhIL-11。结果治疗组Plt<50×109/L持续时间(2.5d)明显少于对照组(5.1d),差异有显著性(P<0.01);治疗组血小板恢复正常,既Plt>100×109/L所需时间(5.9d)明显少于对照组(13.5d),差异有显著性(P<0.01);停药后血小板数量并未明显回落,能稳定在正常水平。结论重组人白细胞介素-11(rhIL-11)是一种有效、安全的治疗化疗后血小板减少的药物。     

白细胞介素-11治疗化疗所致血小板减少的临床观察

化疗是治疗中、晚期癌症患者的主要措施之一，为了提高疗效，临床上有时需要提高治疗强度，增加用药剂量，尤其是对化疗敏感的恶性肿瘤。但是，随着治疗强度的提高，随之而来不同程度的骨髓抑制却无法避免，如急性或迟发性血小板减少症、严重的粒细胞减少症等，这也是造成患者死亡的原因之一。血小板的恢复     

重组人白细胞介素-11治疗实体瘤化疗所致的血小板减少症的随机对照研究

目的:观察重组人白细胞介素-11(rhIL-11)治疗实体瘤化疗所致的血小板减少症的客观疗效;观察rhIL-11在人体的不良反应及其安全性.方法:本研究采用随机对照试验,55例化疗后血小板低于50×109/L的患者,随机分为A组和B组,A组接受rhIL-11,B组不接受rhIL-11治疗.主要观察IL-11能否治疗化疗引起的血小板减少症.结果:A组血小板值在第2～21d均高于B组,第4～21天差别具有显著的统计学意义;A组Ⅱ°、Ⅲ°及Ⅳ°血小板减少的持续天数分别为3.0d、3.2d及0.4d,B组分别为5.1d、5.8d及2.2d,A组血小板减少持续天数短于B组,但无统计学差异.IL-11的不良反应主要包括:心悸、心律失常、水肿、发热、关节肌肉疼痛、注射局部疼痛、皮疹、头痛头晕、乏力等.大多较轻,可以耐受.结论:rhIL-11能刺激血小板增生,治疗化疗引起的血小板降低,是一种有效、安全的治疗血小板减少的药物,值得进一步研究.     

基因重组人白细胞介素-11治疗恶性肿瘤化疗所致血小板减少症的临床探讨

目的观察基因重组人白细胞介素-11(rhIL-11)治疗恶性肿瘤化疗所致血小板减少症的临床疗效及不良反应。方法本组51例患者随机分为治疗组(27例)和对照组(24例)。治疗组病例化疗后外周血血小板计数≤50×109/L时,给予rhIL-11 1.5 mg皮下注射,1/d,连续用药5~14 d,平均9.2 d;当外周血血小板升至≥100×109/L时停用rhIL-11观察血像。对照组病例仅以输注血小板及对症治疗为主。结果治疗组患者应用rhIL-11前后自身比较血小板计数最低值显著升高,差异有显著性(P<0.01);治疗组患者化疗后应用rhIL-11血小板计数最低值较对照组化疗后的最低值显著升高,差异也有显著性(P<0.01);治疗组应用白介素-11后血小板计数低于5.0×109/L的天数比对照组明显缩短,两者比较差异也有显著性(P<0.01)。共治疗27例恶性肿瘤化疗所致的血小板减少症,显效9例(33.3%),有效18例(66.7%)。结论在恶性肿瘤化疗所致的血小板减少症的治疗中,rhIL-11的升血小板作用显著、安全、经济实用。     

重组人白细胞介素-11治疗消化道肿瘤化疗后血小板减少症的临床研究

Objective: To evaluate the efficacy and safety of recombinant human interleukin-11 (rhIL-11) for the chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer. Methods: It was an opened and non-randomized controlled clinical study. When the platelet counts was under 75 × 109/L after chemotherapy, rhIL-11 was administered 25six patients were enrolled into this study. The treatment group and the control group had thirty-eight cases, respectively. The mean recovery time to PLT ≥ 100 × 109/L was 8.1 days in treatment group, while in control group was 12.2 days (P ＜ 0.01).Moreover, the mean recovery time from PLT ≤ 50 × 109/L to ≥ 100 × 109/L was 8.9 days in treatment group, while in control group was 12.9 days (P ＜ 0.05). There was a statistical difference between the two groups. Major side effects included edema,fever, articular muscle soreness, but they were all mild and well tolerable. Conclusion: rhIL-11 can be safely and effectively used for the treatment of chemotherapy-induced thrombocytopenia in patients with gastrointestinal cancer.     

重组人白细胞介素-11预防化疗所致血小板减少的临床研究

目的　评价国产重组人白细胞介素 11(rhIL 11)预防肿瘤化疗患者血小板减少的疗效及不良反应。方法　采用随机双盲自身交叉对照研究方法 ,将试验药品和安慰剂分为A药和B药 ,入选患者随机分为AB组或BA组。在化疗结束后 2 4h开始用药 ,2 5 μg kg体重 ,皮下注射 ,每日 1次 ,连续用药 7～ 14d或至血小板计数≥ 30 0× 10 9 L。结果　有 118例可评价疗效。rhIL 11可显著升高化疗后血小板最低值和化疗第 2 1天血小板值 ,升高幅度分别达 6 0 .7%和 86 .1% (P <0 .0 0 1) ;治疗周期出现血小板减少 (<10 0× 10 9 L)的持续时间为 1.0± 2 .0d ,而对照周期为 6 .9± 5 .4d。主要不良反应为注射部位疼痛 (2 4 .6 % )、红肿 (16 .1% )、硬结 (11.9% )、结膜充血 (16 .1% )、水肿 (8.5 % )、心悸(6 .8% )、乏力 (5 .1% )等 ,大都程度较轻 ,无其他严重不良反应。结论　rhIL 11具有明显的促血小板生成作用 ,可显著减少肿瘤患者化疗后血小板减少的发生 ,缩短血小板减少的持续时间。不良反应较轻且较易处理。     

肺癌合并免疫性血小板减少症1例

肺癌病人出现血小板减少多考虑为化疗所致毒副作用;而免疫性血小板减少症为自身免疫性疾病,二者同时发生在一例患者身上相对少见,本文将哈尔滨医科大学附属第三医院曾诊治的肺癌合并免疫性血小板减少症一例报道如下。     

Irinotecan-induced immune thrombocytopenia

Background: Irinotecan is currently used as second-line chemotherapy for advanced colorectal cancer. We report a case of severe thrombocytopenia after Irinotecan, suggesting an immune mechanism, in a 53-year-old patient.Patients and methods: The patient's sera were screened for platelet antibodies with an indirect platelet immunofluorescence test (PIIFT). The monoclonal antibody immobilization of platelet antigen assay (MAIPA) was used to characterize the antibody target.Results: We detected an IgG platelet antibody in the patient's serum in the presence of Irinotecan by means of PIIFT, and not in the presence of SN-38, its active metabolite. The specificity of the binding was asserted after CD32 MoAb blockade. The platelet binding site could not be strictly identified with MAIPA and immunoblotting but GpIIb/IIIa can be excluded after experiments with Glanzmann platelets.Conclusion: This case can be considered the first documented Irinotecan-induced immune thrombocytopenia.     

Simultaneous Increase in Serum Levels of IL-37 and IL-18 Binding Protein In Low-Grade and High-Grade Brain Tumors

Background: IL-18binding protein (IL-18BP) might play a role in tumor escape from immune surveillance through interacting with IL-37. Such interactions modulate the antitumor activity of IL-18 and affect regulatory T cell (Treg) function. However, the biological roles of IL-37 and IL-18BP have not yet been explored in brain tumors. This study aimed to investigate serum levels of IL-37 and IL-18BP in high-grade and low-grade brain tumors and determine their associations with pathological characteristics of the patients. Subjects and methods: This case-control study consisted of 60 patients with brain tumors (40 low-grade and 20 high-grade) and 30 healthy controls. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure the levels of IL-37 and IL-18BP in serum. Results: Our results indicated that serum levels of IL-37 and IL-18BP were significantly higher in patients with brain tumors (109.02, 426.37 pg/mL), high-grade (104.44, 428.87 pg/mL), and low-grade (113.88, 426.37 pg/mL) tumors in compared to healthy controls (35.03, 362.00 pg/mL), (P<0.05). Interestingly, our results revealed a significant positive correlation between IL-37 and IL-18BP serum levels in brain tumors (n=60, R=0.42, P=0.001). Our study also showed that serum levels of IL-37 and IL-18BP in glioblastoma grade IV were approximately similar to those in astrocytoma grade II, meningioma type I, and pituitary adenoma. Furthermore, no significant differences were found in serum levels of IL-37 and IL-18BP between patients with low-grade and high-grade tumors (P=0.24 and P=0.61, respectively). Conclusion: The simultaneous increase in IL-37 and IL-18BP serum levels and their positive correlation may facilitate disease progression in low-grade and high-grade brain tumors by inhibiting antitumor immune responses.     

结直肠癌患者IL-35和IL-37水平表达与其病理学特征及预后的相关性

目的探讨结直肠癌术后患者白细胞介素35(IL-35)和白细胞介素37(IL-37)水平表达与其病理学特征及预后的相关性。方法选取60例结直肠癌患者作为研究对象,所有患者均行手术治疗,另取同期60例良性结直肠肿瘤手术患者进行比较分析,分析良性肿瘤患者与恶性肿瘤患者IL-35和IL-37水平表达。通过对60例结直肠癌患者的IL-35和IL-37检测,分析IL-35、IL-37水平与结直肠癌临床病理特征的关系,并分析其预后价值。结果与良性肿瘤患者相比,恶性肿瘤患者IL-35水平显著升高,IL-37水平降低(P<0.05);IL-37高表达与低表达的结直肠癌患者TNM分期、分化程度以及有无淋巴结转移情况具有明显差异(P<0.05)。Spearman相关分析结果显示:IL-35与结直肠癌TNM分期和淋巴结节转移均呈显著正相关,与分化程度呈显著负相关(P<0.05);IL-37与结直肠癌TNM分期和淋巴结节转移均呈显著负相关,与分化程度呈显著正相关(P<0.05);多因素分析显示:肿瘤侵袭深度和IL-35为结直肠癌患者术后生存预测的独立指标(P<0.05),其他因素分析对比无显著差异(P>0.05);单因素生存分析显示,TNM、肿瘤侵袭深度、淋巴结转移可作为结直肠癌患者预后预测指标(P<0.05),IL-35不可以作为结直肠癌患者预后预测指标(P>0.05)。结论IL-35和IL-37的水平表达与结直肠癌患者的疾病发展有着明显相关性,在预后相关性上,IL-35水平可能可以作为结直肠癌患者术后预测的独立指标。     

The balance of serum IL-18/IL-37 levels is disrupted during the development of oral squamous cell carcinoma

Growing evidences have demonstrated a pivotal role of chronic inflammation in oral squamous cell carcinoma (OSCC) through the modulation of inflammatory cells and cytokine production. IL-37 is newly discovered anti-inflammatory member of IL-1 family and can bind to IL-18 receptor to inhibit IL-18 (pro-inflammatory member of IL-1 family) function. Investigation on the balance of IL-18/IL-37 would provide new insights into the function of IL-1 family in OSCC. Thus, serum IL-18 and IL-37 levels of OSCC patients (n = 108), leukoplakia patients (n = 40), and healthy donors (n = 36) were collected to analyze the balance of IL-18 and IL-37, and also determine their diagnostic value and prognostic significance in OSCC. The results showed that OSCC patients had high IL-18 and low IL-37 levels in serum and peripheral blood mononuclear cell (PBMC). The ratio of IL-18/IL-37 in serum efficiently distinguished non-cancer individuals from OSCC patients (cut off value: 2.15). Moreover, patients with high IL-18 and low IL-37 were susceptible to develop advanced tumor stage and lymph node metastasis (Odd ratios of IL-18/IL-37 is 4.903 and 12.613, respectively). Meanwhile, higher IL-18/IL-37 ratio could predict shorter overall survival and disease-free survival of OSCC patients, although it was not an independent prognostic factor. We further analyze the correlations of serum IL-18/IL-37 with immunocytes in peripheral blood and found that high IL-18 level was associated with more CD19⁺ B cells, while serum IL-37 seem to be associated with reduced percentage of CD3⁺CD8⁺ T cells, indicating its balance could change the adaptive immune response. Unexpectedly, we first revealed the different function of IL-18/IL-37 in serum and tumor tissues. High mRNA expression of IL-18 in tumor tissues correlated with low lymph node metastasis rate and low tumor stage, which was contradictory to the pro-tumor role of IL-18 in serum. In conclusion, enhanced ratio of IL-18/IL-37 level in serum could be an efficient biomarker for OSCC. Its balance might regulate CD19⁺ B cells and CD3⁺ CD8⁺ T cells for OSCC progression.     

Successful treatment of non‐Hodgkin lymphoma associated immune thrombocytopenia with involved field radiotherapy

Immune thrombocytopenia complicates the course and impacts the outcome of non‐Hodgkin lymphoma (NHL‐ITP, non‐Hodgkin lymphoma–immune thrombocytopenic purpura). The response to corticosteroids and/or intravenous immune globulins is usually short lasting, but NHL‐ITP usually responds to anti‐lymphoma chemotherapy. It is not clear if this success is due to the elimination of the lymphomatous tissue or to the immunosuppressor/immunomodulator effect of chemotherapy. Myelosuppressive anti‐lymphoma chemotherapy carries the risk of severe thrombocytopenia that may not respond adequately to platelet transfusion support. We report on a patient with recurrent diffuse large B‐cell lymphoma that coincided with immune thrombocytopenia. Both diseases completely responded to involved field radiation therapy. This supports the hypothesis that at least in some cases of NHL‐ITP, the lymphomatous clone secretes the anti‐platelet antibodies. This supports the therapeutic decision making for these patients. Copyright © 2013 John Wiley & Sons, Ltd.     

Polymorphism Analysis of Interleukin-18 and Interleukin-37 Genes in Hepatitis B Infections with Different Outcomes: A Preliminary Report from an Iranian Population

Objective: Given the vital role of cytokines in influencing the outcomes of hepatitis B virus (HBV) infections, this study aimed to investigate the association between polymorphisms of interleukin (IL)-18 and IL-37 and the outcomes of HBV infection. Methods: In this study, we enrolled 300 subjects with chronic HBV infection, including those with cirrhosis/hepatocellular carcinoma (C/HCC), chronic active hepatitis B (CAH) infection, or asymptomatic carriers (AC), and 58 individuals whose infection was spontaneously cleared (SC). Genomic DNA was extracted, and IL-18/IL-37 genotyping was performed using PCR-RFLP and ARMS-PCR. Results: The frequency of genotypes and alleles of IL-18 single nucleotide polymorphisms (SNPs) at positions rs1946519, rs1946518, and rs187238 and IL-37 at position rs4241122 were not statistically different among the four studied groups (P>0.05). Furthermore, the frequency of different haplotypes was similar among the studied groups (P>0.05). Conclusions: Polymorphisms of IL-18 SNPs at positions rs1946519, rs1946518, and rs187238 and variation of IL-37 at position rs4241122 do not appear to influence the outcome of HBV infection.     

Expression and Regulation of Interleukin-37 in Pathogenesis of Nasal Polyps

Interleukin-37 (IL-37) belongs to IL-1 family and is recently identified as a natural suppressor of innate inflammatory and immune responses. Its role in digestive system was well characterized, however, little is known about its function in respiratory diseases. This study is aimed to investigate the expression and regulation of IL-37 in patients with nasal polyps (NPs). Twenty-five patients with NPs and sixteen normal controls were included, and IL-37 production was determined by immunohistochemistry and enzyme-linked immuno sorbent assay, respectively. The relationship between IL-37 expression and Th1/Th2 cytokines was also evaluated. Besides, the effect of IL-37 on dispersed nasal polyp cells (DNPCs) was investigated. We observed significantly decreased IL-37 mRNA and protein levels expression in NPs compared with normal control. IL-37 was found negatively with Th2 cytokines and had no relation with Th1 cytokines. Furthermore, we provided the first evidence that IL-37 down-regulates Th2 cytokine expressed by DNPCs. Our results demonstrate that enhanced Th2 cytokine levels was related to decreased IL-37 expression in NPs, and provide a possible explanation for IL-37’s regulatory role in the pathogenesis of NPs.     

Circulating immune complexes in chronic myeloid leukemia: Studies on 37 K protein antigen

The 37 K protein, earlier found to be present in 3.75% PEG-precipitates from sera of untreated patients with CML, was further characterized. Gel filtration at neutral pH resolved the PEG-precipitate into a non-IgG containing protein peak-I and a IgG containing peak-II. Immunoprecipitation of peak-II with antihuman IgG antiglobulin and subsequent 2D-SDS-PAGE analysis of the immunoprecipitate revealed the presence of 37 K protein in peak-II confirming its association with IgG.

¹²⁵I-37 K protein was found to interact with antibodies isolated from autologous and allogenic CML-CIC samples but not with similarly isolated antibodies from normal subject, and patients with AML, ALL, MF, and HD. Peptide maps generated by tryptic digestion of 37 K protein (from five different CML patients) were found to be identical.

Specific interaction of 37 K protein with the autologous and allogenic antibodies and identity of peptide maps lead to the conclusion that the 37 K protein is a CML-associated antigen appearing in CIC.     

肺癌患者IL－2RmRNA表达的临床意义

制备了人ＩＬ－２ＲａｃＤＮＡ探针，采用斑点印迹杂交法对４６例肺癌患者外周血单个核细胞（ＰＢＭＣ）ＩＬ－２ＲｍＲＮＡ的表达水平进行研究。结果发现ＩＬ－２ＲｍＲＮＡ的表达程度与肿瘤转移关系密切。肺癌无转移组：ＩＬ－２ＲｍＲＮＡ表达显著高于对照组与转移组（Ｐ＜０．００１），且与患者的组织学类型及病期有明显关系。转移组：ＩＬ－２Ｒ表达显著低于对照组（Ｐ＜０．００１），提示此组病人存在免疫抑制．其抑制可能存在细胞活化阶段或ＩＬ－２Ｒ的转录水平。同期所测血清肿瘤坏死因子（ＴＮＦ）在两组患者无明显差异。本组结果提示：ＩＬ－２ＲｍＲＮＡ表达水平与患者预后密切相关。     

IL-12调控胃癌细胞凋亡及免疫逃逸因子分泌机制探讨

目的 探讨白细胞介素-12(IL-12)调控胃癌细胞凋亡及免疫逃逸因子分泌的途径.方法 培养胃癌SGC7901细胞,随机分为空白对照组、感染阴性对照(NC)腺病毒的NC腺病毒组、感染IL-12腺病毒的IL-12腺病毒组、转染NC质粒的NC质粒组、转染STAT4质粒的STAT4质粒组、转染NC siRNA的si-NC组、...