Interleukins as new prognostic genetic biomarkers in non-small cell lung cancer

Background

Surgery is the standard treatment for early-stage NSCLC, and platinum-based chemotherapy remains as the treatment of choice for advanced-stage NSCLC patients with naïve EGFR status. However, overall 5-years relative survival rates are low. Interleukins (ILs) are crucial for processes associated with tumor development. In NSCLC, IL1B, IL6, IL12A, IL13 and IL16 gene polymorphisms may contribute to individual variation in terms of patient survival. The purpose of this study was to evaluate the association between IL gene polymorphisms and survival in NSCLC patients.

巴豆醛致雄性大鼠神经毒性作用的研究

目的探讨巴豆醛暴露致雄性大鼠神经毒性作用,分析其可能的作用机制。方法于2019年7至10月,将24只SPF级雄性Wistar大鼠随机分为对照组和2.5、4.5、8.5 mg/kg染毒组,每组6只,分别经口给予0.0、2.5、4.5、8.5 mg/kg体重巴豆醛溶液,每周5次,连续染毒90 d。染毒结束后,测量大鼠体重,麻醉解剖取大鼠大脑组织和肝组织。测定大脑组织乙酰胆碱酯酶(AChE)活力及肝组织乙酰胆碱(ACh)水平;检测大脑组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力以及丙二醛(MDA)和还原型谷胱甘肽(GSH)水平;酶联免疫吸附测定(ELISA)法检测大脑组织中白细胞介素6(IL-6)、白细胞介素1β(IL-1β)、肿瘤坏死因子α(TNF-α)水平。结果与对照组比较,2.5、4.5、8.5 mg/kg染毒组大鼠大脑组织中AChE活力明显降低,8.5 mg/kg染毒组大鼠肝组织中ACh水平明显升高,差异均有统计学意义(P<0.05);与对照组比较,4.5、8.5 mg/kg染毒组大鼠大脑组织中MDA水平明显升高,GSH水平和SOD、GSH-Px活力明显降低,差异均有统计学意义(P<0.05);与对照组比较,2.5、4.5、8.5 mg/kg染毒组大鼠大脑组织中TNF-α、IL-6水平明显升高,4.5、8.5 mg/kg染毒组IL-1β水平明显升高,差异均有统计学意义(P<0.05)。结论巴豆醛暴露可致大鼠神经系统损伤,可能与氧化平衡状态改变及上调大脑组织炎性因子表达等作用有关。     

重症肌无力患者白细胞介素17、21、23检测及其临床意义

目的 检测重症肌无力患者血清白细胞介素（IL）-17、21、23的表达水平,探讨IL-17、IL-21和IL-23水平与重症肌无力发病的关系.方法 采用酶联免疫分析法检测45例重症肌无力患者血清IL-17、IL-21和IL-23水平,并与正常对照组比较.结果 重症肌无力组IL-17、IL-21和IL-23水平高于对照组（重症肌无力组IL-17、IL-21和IL-23中位数分别为5.86 pg/ml、198.15 pg/ml、224.04 pg/ml,对照组中位数分别为5.20 pg/ml、80.27 pg/ml、59.46 pg/ml）,差异具有统计学意义（P＜0.05）.眼肌型与全身型相比IL-17、IL-21、IL-23水平无显著性差异（P＞0.05）.胸腺疾病组与非胸腺疾病组IL-17、IL-21、IL-23水平无显著性差异（P＞0.05）.结论 IL-17、IL-21和IL-23在重症肌无力发病的免疫调节过程中发挥一定作用.     

Do repeated runs of a cell saver device increase the pro-inflammatory properties of washed blood?

OBJECTIVE: Intra-operative cell salvage is increasingly used, especially in longer cases with continuing blood loss. However it is unknown if the quality of processed blood is affected when larger quantities of blood are processed. We hypothesized that the quality of the washed blood decreases after multiple runs. METHODS: Intra-operative cell salvage was performed in 42 consecutive patients undergoing cardiac surgery. When 1250 ml of blood was collected in the blood collection reservoir, this was processed and returned to the patient. In 21 patients more than 2500 ml of blood was collected during the whole procedure, thus allowing at least two subsequent runs with the auto-transfusion device. Blood samples were drawn from the blood collection reservoir of the cell saver device before, and from the processed blood after each run. RESULTS: After the first run interleukin-6 concentrations were reduced with 85% (from 21+/-35 microg/l to 3.1+/-4.4 microg/l), whereas after the second run 72% was removed (63+/-69 microg/l to 17.6+/-25.3 microg/l). Leukocyte counts almost doubled after both processing runs (from 2.6+/-1.5 x 10(9)/l to 5+/-3.6 x 10(9)/l) and from 3.9+/-2.2 x 10(9)/l to 7.7+/-5.9 x 10(9)/l), hemoglobin concentration (14.8+/-1.6 mmol/l vs 15.0+/-1.1 mmol/l), free hemoglobin (2.3+/-1.6g/l vs 2.1+/-1.4 g/l) and platelet counts (18+/-9 x 10(9)/l vs 28+/-23 x 10(9)/l) were not different between the two runs. CONCLUSIONS: Our results suggest, based on interleukin-6 and free hemoglobin washout that the quality of the processed blood remains constant with multiple runs of the cell saver device.     

白介素家族在急性格林-巴利综合征发病机制中的作用

细胞因子在急性格林-巴利综合征(GBS)发病机制中所起的作用越来越重要,尤其是白介素(IL)在急性格林-巴利综合征发病过程中所起的促炎、抑炎作用越来越重要。近期研究表明IL-12、IL-17、IL-22在急性GBS的发病过程中起着重要的促炎作用,IL-35、IL-37起着重要的抑炎作用。本文对IL-17、IL-22、IL-35、IL-37、IL-9在急性GBS发病机制中所起的作用加以总结。     

白细胞介素-33的测定及其与早期类风湿关节炎相关性的研究

目的 通过检测早期类风湿关节炎(RA)患者血清中的白细胞介素(IL)-33水平,分析其与早期RA之间的相关性.方法 收集病程<1年的早期RA患者100例,骨关节炎(OA)患者40例以及健康对照者70名.采用双抗体夹心酶联免疫吸附试验(ELISA)测定血清中的IL-33水平,并分析血清IL-33水平与RA各临床和实验室指标的相关性.计量资料的比较采用Kruskal-Wallis检验和(或)Mann-Whitney U检验,计数资料比较采用X2检验,相关性分析采用Spearman相关分析.结果 RA患者血清IL-33水平为(282±871)pg/ml,显著高于健康对照组[(7±38)pg/ml,P(0.01)和OA患者[(8±35)pg/ml,P<0.01].血清IL-33水平与类风湿因子(RF)、隐性类风湿因子IgG(HRF-IgG)、抗环瓜氨酸肽(CCP)抗体、抗突变型瓜氨酸化波形蛋白(MCV)抗体呈正相关(r分别为:0.312,0.277,0.213,0.302,P<0.01或P<0.05). IL-33阳性组患者的RF阳性率、HRF-IgG阳性率、抗CCP抗体阳性率、抗MCV抗体阳性率(86%、31%、86%、94%)较IL-33阴性组患者(54%、11%、42%、72%)显著升高(P均<0.05). 结论 IL-33在RA患者血清中显著升高,并与多种自身抗体(包括RF、抗CCP抗体、抗MCV抗体和HRF-IgG)显著相关,可能是RA预后不良的因素之一.     

冠心病患者血浆白细胞介素10、18和C反应蛋白的变化及其意义

目的:探讨血浆白细胞介素(IL)-10,IL-18和C反应蛋白(CRP)在冠心病(CHD)发病过程中的作用及其临床意义。方法:采用酶联免疫双抗体夹心法(ELISA)对106例CHD患者[急性心肌梗塞(AMI)36例,不稳定型心绞痛(UAP)30例,稳定型心绞痛40例(SAP)]和32例正常人血浆中IL-10,IL-18和CRP的浓度进行检测。并根据Gensini积分,106例CHD患者又被分为A组(Gensini积分26分)、B组(Gensini积分26~54分)和C组(Gensini积分54分),对各组上述指标进行比较。结果:CHD患者的SAP组、UAP组、AMI组血浆IL-10水平依次为[(115.56±53.11)pg/ml、(86.00±30.55)pg/ml、(72.38±19.55)pg/ml],IL-18水平依次为[(217.53±95.83)pg/ml、(327.93±80.36)pg/ml、(430.28±71.62)pg/ml]和CRP水平依次为[(0.61±0.38)mg/L、(0.84±0.44)mg/L、(1.72±0.67)mg/L],均分别显著高于正常对照组[(49.58±19.82),(154.97±88.65),(0.46±0.34)mg/L,P均0.05]。冠心病C组血浆IL-18(389.21±93.55),CRP(0.86±0.48)水平明显高于B组[(331.32±106.59),(0.62±0.38)]及A组[(250.20±106.89),(0.42±0.34)];B组的显著高于A组的(P均0.05)。结论:虽然IL-10作为冠心病的保护因子水平升高,但不足以阻止冠心病的发生、发展,IL-18和CRP水平与冠心病的发生发展相关,其水平的检测对冠心病诊断及病情判断有重要意义。     

黄芪桂枝五物汤对胶原诱导性关节炎大鼠血清中白细胞介素-20的影响

目的观察黄芪桂枝五物汤对胶原诱导性关节炎(CIA)大鼠的一般情况、体质量、血红蛋白、血清中白细胞介素-20(IL-20)水平的影响,以阐明黄芪桂枝五物汤治疗类风湿关节炎的作用机制。方法选用健康清洁级SD大鼠32只,随机分为4组,正常对照组、模型组、雷公藤多苷组、黄芪桂枝五物汤组。除正常对照组外,其余各组均行CIA大鼠模型。观察造模后大鼠一般情况及造模后第1、2、3、4周的体质量变化情况;采用全自动血细胞分析仪测定各组大鼠血红蛋白含量,采用酶联免疫吸附试验(ELISA)方法测定各组大鼠血清中IL-20的水平。结果造模后第1、2、3周大鼠体质量各组之间差异无统计学意义(P>0.05),造模后第4周模型组体质量低于正常对照组、雷公藤多苷组、黄芪桂枝五物汤组,差异有统计学意义(P<0.05)。治疗1个月后,与正常对照组相比,模型组大鼠血清中IL-20水平升高,差异有统计学意义(P<0.05);与模型组比较,黄芪桂枝五物汤组血红蛋白水平高于模型组,差异有统计学意义(P<0.05);经雷公藤多苷、黄芪桂枝五物汤治疗后大鼠血清中IL-20的水平下降,差异有统计学意义(P<0.05);雷公藤多苷组、黄芪桂枝五物汤组血清IL-20差异无统计学意义(P>0.05)。结论黄芪桂枝五物汤能升高CIA大鼠血红蛋白含量,有抑制CIA大鼠血清中IL-20升高的作用。     

IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-γ are not

Psoriasis is a common chronic skin disease with a largely unknown pathogenesis. We demonstrate here that transgenic over-expression of interleukin (IL)-22 in mice resulted in neonatal mortality and psoriasis-like skin alterations including acanthosis and hypogranularity. This cutaneous phenotype may be caused by the direct influence of IL-22 on keratinocytes, since this cytokine did not affect skin fibroblasts, endothelial cells, melanocytes, or adipocytes. The comparison of cytokines with hypothesized roles in psoriasis pathogenesis determined that neither interferon (IFN)-γ nor IL-17, but only IL-22 and, with lower potency, IL-20 caused psoriasis-like morphological changes in a three-dimensional human epidermis model. These changes were associated with inhibited keratinocyte terminal differentiation and with STAT3 upregulation. The IL-22 effect on differentiation-regulating genes was STAT3-dependent. In contrast to IL-22 and IL-20, IFN-γ and IL-17 strongly induced T-cell and neutrophilic granulocyte-attracting chemokines, respectively. Tumor necrosis factor-α potently induced diverse chemokines and additionally enhanced the expression of IL-22 receptor pathway elements and amplified some IL-22 effects. This study suggests that different cytokines are players in the psoriasis pathogenesis although only the IL-10 family members IL-22 and IL-20 directly cause the characteristic epidermal alterations. Kerstin Wolk and Harald S. Haugen equally contributed to this work.     

The role of salivary cytokine biomarkers in tongue cancer invasion and mortality

Squamous cell carcinoma of the tongue (TSCC) has one of the poorest prognoses of head and neck cancers. This study aims to improve early detection of the disease by identifying salivary biomarkers that can identify a spectrum of patients progressing from high-risk to TSCC. We also examine the mortality of exophytic and endophytic TSCC, expecting the elevated cytokine levels in endophytic patients to be associated with a shorter survival. Saliva was collected from patients with TSCC and controls and cytokine protein levels were measured. Specimens were collected from the Los Angeles County (LAC) + University of Southern California (USC) and USC University Hospital clinics. A convenience sample of patients with TSCC was divided into endophytic (n=10) and exophytic (n=8) cancer by physician diagnosis. Controls were divided into 4 groups of 14 based on their high-risk smoking and drinking behaviors. Main outcome measures: The levels of IL-1α, IL-6, IL-8, VEGF-a and TNF-α in saliva were measured using quantitative ELISA and compared using two-way ANOVA. All five cytokines were elevated in the endophytic TSCC group compared to other groups, which correlated with the decreased survival rate (10.4 months) in this group compared to exophytic TSCC (24 months). IL-1α, IL-6, TNF-α and VEGF were also elevated in the exophytic TSCC group compared to smoking-drinking controls. Salivary levels of IL-1α, IL-6, IL-8, VEGF-a and TNF-α can identify the progression of TSCC from high-risk to neoplasm, serving as potential biomarkers for cancer screening and early detection. The correlation with survival implies a prognostic benefit and could serve as a tool for management decisions and future treatment targets.