胺碘酮对心力衰竭患者细胞因子的影响

目的观察心力衰竭患者血清肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的变化,以及胺碘酮对心力衰竭患者外周血单核细胞(PBMC)分泌上述细胞因子的影响。方法测定30例健康人(对照组)和40例心力衰竭患者血清TNF-α和IL-6浓度,离心取PBMC,分别加入胺碘酮和脂多糖诱导(胺碘酮浓度为0μmol/L、0.1μmol/L、1.0μmol/L和10μmol/L,并进行细胞培养,经48小时孵化后,取培养上清液,用酶联免疫吸附法测定培养上清液中TNF-α和IL-6的浓度。结果与正常对照组相比,心力衰竭患者血清TNF-α和IL-6浓度明显升高,并随心力衰竭的程度加重而增加,TNF-α与IL-6呈正相关(r=0.61,P<0.01),胺碘酮对PBMC分泌的TNF-α和IL-6具有抑制作用并呈剂量依赖性。结论心力衰竭患者血清TNF-α与IL-6浓度明显升高,胺碘酮能抑制心力衰竭患者细胞因子的生成。TheeffectofAmiodaroneonserumcytokinelevelsinpatientswithchronicheartfailure     

心力衰竭患者炎性与抗炎性细胞因子表达的平衡失调

目的 :了解炎性与抗炎性细胞因子在充血性心力衰竭 (CHF)过程中的变化及其临床意义。方法 :用双抗体夹心ELISA法测定 12 2例CHF患者及 30例健康人血浆中肿瘤坏死因子 α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 10 (IL 10 )的浓度。结果 :①CHF患者血浆中TNF α水平明显高于对照者 (P <0 .0 5或 <0 .0 1) ,且随着心力衰竭程度的加重 ,TNF α水平呈进行性增高 ;CHF患者血浆IL 6及IL 10水平 ,心功能Ⅲ、Ⅳ级者明显高于对照者 (P <0 .0 5或 <0 .0 1) ,而心功能Ⅱ级者与对照者相比差异无显著性意义。②TNF α与IL 6 (r =0 .6 18,P <0 .0 1)、IL 10 (r =0 .5 6 6 ,P <0 .0 1)均呈正相关 ,但TNF α与IL 10的比率 (TNF α/IL 10 )也随着心功能的恶化而升高 ,IL 10的升高与TNF α的升高相比明显不足。结论 :细胞因子的变化与心力衰竭的严重程度密切相关 ,CHF患者血中炎性细胞因子明显升高的同时伴有抗炎性细胞因子升高的相对不足 ,炎性与抗炎性细胞因子之间的平衡失调可能参与了CHF的发生发展     

充血性心力衰竭炎性细胞因子的改变

目的 :探讨充血性心力衰竭 (CHF)时肿瘤坏死因子 α(TNF α)、白细胞介素 6 (IL 6 )、白细胞介素 1β(IL 1β)和一氧化氮 (NO)的变化 ,及其与CHF关系。 方法 :CHF患者 4 5例和年龄匹配的对照者 17例 ,根据NY HA分级将CHF患者分成Ⅱ、Ⅲ、Ⅳ级 3组 ;根据体重分成恶病质组及非恶病质组。用酶联免疫法测定IL 6 ,用放射免疫法测定IL 1β、TNF α ,用比色法测定NO。 结果 :CHF组血清IL 6、IL 1β、TNF α和NO较对照组明显升高 ,IL 6、NO在心功能Ⅱ、Ⅲ、Ⅳ级时均显著升高 ,TNF α在Ⅲ、Ⅳ级时显著升高 ,而IL 1β在Ⅳ级时才显著升高。不同病因的CHF之间差异无统计学意义 ,恶病质组及非恶病质组之间差异也无统计学意义。血清TNF α与IL 6呈正相关 (r =0 .5 82 9,P <0 .0 1)。结论 :血清IL 6、IL 1β、TNF α、NO水平与CHF的严重程度密切相关 ,可作为判断CHF严重程度的指标 ;IL 6、IL 1β、TNF α在CHF的发生发展中可能起重要作用     

卡托普利对慢性心力衰竭患者单核细胞分泌细胞因子的影响

本研究旨在了解慢性心力衰竭 (CHF)患者外周血单核细胞 (PBMC)分泌肿瘤坏死因子α(TNF α)、白细胞介素 6(IL 6)和白细胞介素 1β(IL 1β)水平的变化 ,并观察卡托普利对这些细胞因子分泌的影响。1.资料与方法 :CHF组 3 5例 ,按NYHA心功能分级标准分为Ⅱ、Ⅲ、Ⅳ级组 ,符合Framingham心力衰竭诊断标准 ,并除外近期感染、风湿活动、自身免疫性疾病、恶性肿瘤和应用免疫制剂者。健康对照组 12例 ,其性别、年龄和白细胞计数均与CHF组相匹配。采用Ficoll Hypaque密度梯度离心法分离PBMC ,利用贴壁法纯化细胞。将PBMC重悬于RPMI…     

培哚普利长期治疗对充血性心力衰竭患者血清细胞因子水平的影响

目的　探讨长期使用培哚普利治疗充血性心力衰竭 (CHF)患者后血清细胞因子水平变化的意义。方法　选择长期或短期使用培哚普利的缺血性与高血压性CHF患者各 32例、30例 ,正常对照组 30例 ,测定血清肿瘤坏死因子(TNF α)、白细胞介素 - 6 (IL 6 )水平并作比较。结果　CHF患者血清TNF α、IL 6水平明显高于正常对照组 (P <0 0 1) ,CHF长期使用培哚普利组TNF α、IL 6水平低于短期组 (P <0 0 5 )。结论　培哚普利可能直接或间接降低血清TNF α、IL 6水平 ,有利于改善心肌重构     

充血性心力衰竭患者血清IL-1β变化及胺碘酮对PBMC分泌IL-1β的影响

近年来,细胞因子参与心肌细胞收缩功能的调节及其在充血性心力衰竭(CHF)发生发展中的作用已受到国内外学者的关注,但其确切机制尚不明确。胺碘酮等抗心律失常药物对CHF的有益作用已见报道,但其作用机制亦不清楚。本研究测定CHF患者的血清IL-1β水平,并观察胺碘酮对CHF患者外周血单个核细胞(PBMC)分泌IL-1β的影响,以探讨IL-1β在CHF发生发展中的作用及胺碘酮对CHF的作用机制。1　资料与方法1.1　临床资料　观察组为CHF患者20例,根据纽约心脏病学会(NYHA)心功能分级标准,分为心功能级10例,男7例、女3例,年龄61.2±6.1(48～69)…     

白细胞介素-10在川崎病炎性细胞因子介导的血管损伤中的作用初探

目的　探讨白细胞介素 10 (IL 10 )在炎性细胞因子介导的川崎病血管内皮损伤中的作用及机制。方法　建立人脐静脉内皮细胞培养模型 ,ELISA双抗体夹心法检测川崎病患儿外周血单个核细胞 (PBMC)活化后培养上清IL 6、IL 1β、肿瘤坏死因子 α(TNF α)、IL 10的分泌量 ;AnnexinV/PI双染色法 ,流式细胞仪检测川崎病患儿PBMC培养上清所诱导的内皮细胞凋亡率 ;凝胶电泳迁移率转换实验 (EMSA)检测所活化PBMC核因子NF κB活性。结果　川崎病组患者PBMC体外刺激活化后IL 6、IL 1β、TNF α等炎性细胞因子及IL 10的分泌量均明显高于正常对照组 (P <0 0 1) ,其培养上清所诱导内皮细胞凋亡率 (38 4± 7 8) %较正常组 (2 8± 0 8) %明显升高。抗IL 6、TNF αMcAb、IL 1ra加入川崎病患儿PBMC培养上清 ,可不同程度抑制川崎病患儿PBMC培养上清所诱导内皮细胞的凋亡 ,而抗IL 10McAb加入川崎病患儿PBMC培养上清所诱导内皮细胞的凋亡细胞反而增多 ,凋亡细胞的百分率高达 (5 8 6± 14 6 ) %。川崎病患儿PBMC刺激活化后核因子NF κB活性显著增高。于PBMC培养上清加入IL 10 ,可见伴随着IL 6、IL 1β、TNF α等炎性细胞因子在PBMC中的表达降低 ,NF κB活性也降低 ,同时内皮细胞凋亡明显减少。结论　IL 10抑制川崎病患儿免疫     

培哚普利对老年充血性心力衰竭患者血清炎性细胞因子的影响

目的 观察培哚普利对老年充血性心力衰竭(CHF)患者血清中肿瘤坏死因子(TNF—α)、白细胞介素—1(IL-1β)、白细胞介素-6(IL-6)的影响．方法 放免法检测53例老年CHF患者(培哚普利组28例，常规治疗组25例)治疗前后及25例健康老年人血清中TNF-α、IL-1β、IL—6水平．结果 老年CHF患者血清中TNF—α、IL-1β、IL—6水平显著高于对照组(P＜0．01)，且随着心功能损害程度加重而升高，TNF—α、IL—6水平在心功能各组间比较有显著性差异(P＜0．05)，IL—1β水平在心功Ⅳ级显著高于心功能Ⅱ、Ⅲ级(P＜0．05)．培哚普利组与常规治疗组老年CHF治疗后血清炎性细胞因子浓度均有明显降低，但培哚普利组TNF—α、IL-1β、IL—6水平下降更为明显(P＜0．05)。结论 血清中TNF—α、IL—1β、IL-6水平可反映心力衰竭的程度；培哚普利可明显降低老年CHF患者血清TNF—α、IL-1β、IL—6水平，从而保护和改善心脏功能．     

充血性心力衰竭患者TNF-α和IL-6变化及临床意义

目的 :探讨充血性心力衰竭患者肿瘤坏死因子 (TNF α) ,白细胞介素 6 (IL 6 )的变化及意义。方法 :56例充血性心力衰竭患者和 30例健康体检者为研究对象 ,采用酶联免疫双抗体夹心法测定血清TNF α ,IL 6浓度 ,用二维心脏超声测定左室射血分数 (LVEF)。结果 :1 血清IL 6、TNF α、去甲肾上腺素 (NE)在CHF各组均升高 ,但心功能Ⅱ级组与对照组比较差异不显著 (P >0 0 5) ;心功能Ⅲ级 ,Ⅳ级组IL 6 ,TNF α ,NE明显高于心功能Ⅱ级和对照组 (P均 <0 0 5)。IL 6、TNF α、NE与LVEF呈高度负相关(r=- 0 6 3,P <0 0 1 ;r=- 0 54,P <0 0 5;r=- 0 58,P <0 0 1 )。 2 随心衰程度加重 ,血清TNF α、IL 6和NE浓度越高。TNF α与NE ,IL 6与NE呈明显正相关 (r =0 57,P <0 0 1 ;r =0 51 ,P <0 0 5)。 3 随心衰程度加重 ,血清IL 6与TNF α浓度越高 ,且二者呈正相关 (r =0 39,P <0 0 5)。结论 :CHF患者血清TNF α和IL 6浓度升高 ,尤其中重度CHF患者更加明显 ,并与LVEF呈负相关 ,提示血清IL 6、TNF α水平可作为CHF严重程度的判断与预后指标。     

心力衰竭患者血浆细胞因子的变化及其临床意义

目的　探讨充血性心力衰竭 (心衰 ,CHF)患者血中肿瘤坏死因子 α(TNF α)和白细胞介素 6(IL 6)的变化及其临床意义。方法　双抗体夹心ELISA法测定 12 2例CHF患者及 3 0例健康人血浆中TNF α和IL 6的浓度。超声心动图测量左心室射血分数及左心室舒张末期内径 ,X线胸片测心胸比。结果　CHF患者血浆中TNF α水平明显高于对照组 (P <0 .0 5 ) ,且随着心衰程度的加重 ,TNF α水平呈进行性增高 ;IL 6水平仅在心功能Ⅲ级、Ⅳ级组中明显高于对照组 (P <0 .0 5 )。TNF α、IL 6与左心室射血分数呈负相关 (r =-0 .5 13 ,r =-0 .45 3 ,P <0 .0 1) ,与心胸比呈正相关 (r =0 .5 0 1,r =0 .43 8,P <0 .0 1) ;与左心室舒张末期内径呈正相关 (r =0 .3 42 ,r =0 .3 0 4,P<0 .0 1)。结论　CHF患者TNF α和IL 6升高可能是心功能恶化的免疫学标志之一 ,提示炎症机制参与心力衰竭的进程     

老年急性心肌梗死患者肿瘤坏死因子-α和白细胞介素-10的变化及辛伐他汀的干预作用

目的　探讨老年人急性心肌梗死 (AMI)患者外周循环肿瘤坏死因子 α(TNF α)和白细胞介素 10 (IL 10 )的变化及辛伐他汀对TNF α和IL 10的作用。方法　测定 39例老年AMI患者 (AMI组 )、2 0例老年陈旧性心肌梗死 (OMI)患者 (OMI组 )及 2 0例正常老年人 (正常人组 )血清TNF α和IL 10浓度。 39例AMI患者入院后随机分为辛伐他汀组和对照组 ,治疗前、治疗后 1周和 6周测定血清TNF α和IL 10浓度。结果　AMI组TNF α、IL 10水平明显高于OMI组 ;OMI组TNF α水平明显高于正常人组 ;正常人组血清IL 10未检测到。辛伐他汀组和对照组经治疗后 1周、6周TNF α水平均显著下降 ,6周后辛伐他汀组TNF α水平显著低于对照组。辛伐他汀组和对照组IL 10水平 6周后均显著降低 ,但两组差异无显著性意义。结论　辛伐他汀具有降低AMI患者血清TNF α水平的作用 ,对IL 10水平无影响     

Anti–interleukin‐6 receptor antibody therapy reduces vascular endothelial growth factor production in rheumatoid arthritis

Objective

To investigate whether interleukin‐6 (IL‐6) is a regulator of vascular endothelial growth factor (VEGF) in rheumatoid arthritis (RA).

Methods

Serum VEGF levels in RA patients were assayed before and after 8 weeks or 24 weeks of maintenance therapy with humanized anti–IL‐6 receptor monoclonal antibody (anti–IL‐6R mAb). VEGF secreted by RA synovial fibroblasts cultured in the presence of IL‐6, IL‐1β, and/or tumor necrosis factor α (TNFα) was measured. The inhibitory effect of anti–IL‐6R mAb, recombinant IL‐1 receptor antagonist (IL‐1Ra), and anti‐TNFα mAb on VEGF production was also examined.

Results

Serum VEGF levels in RA patients before anti–IL‐6R mAb therapy were significantly higher than those in healthy controls (P < 0.0005). Treatment of RA patients with anti–IL‐6R mAb normalized serum VEGF levels. In the in vitro study, IL‐6 and IL‐1β each induced a slight amount of VEGF production in synovial cells, but TNFα did not. Although VEGF‐inducing activity of these cytokines was not remarkable when they were added alone, IL‐6 acted synergistically with IL‐1β or TNFα to induce VEGF production. There was no synergistic effect between IL‐1β and TNFα. In the presence of all of these cytokines, anti–IL‐6R mAb eliminated the synergistic effect of IL‐6, IL‐1β, and TNFα, while IL‐1Ra or anti‐TNFα mAb did not.

Conclusion

Anti–IL‐6R mAb therapy reduced VEGF production in RA. IL‐6 is the pivotal cytokine that induces VEGF production in synergy with IL‐1β or TNFα, and this may be the mechanism by which IL‐6 blockade effectively suppresses VEGF production in synovial fibroblasts.

     

Interleukin-6 and tumor necrosis factor-alpha levels increase in response to maximal exercise in patients with chronic heart failure

Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. Strenuous exercise causes activation of both systems but the effect of acute bouts of exercise on cytokines is not known in patients with CHF. This study determined whether maximal exercise induces activation of cytokines in CHF. Plasma interleukin-6 (IL-6), tumor necrosis factor (TNF)-alpha, epinephrine, norepinephrine, and atrial and brain natriuretic peptides (ANP and BNP) were determined before and after symptom-limited cardiopulmonary exercise testing in 80 patients with CHF (LVEF=38+/-1%, peak VO(2)=18.8+/-0.5 ml/min/kg) and age-matched 33 controls. Resting IL-6 (Controls vs. CHF: 1.3+/-0.2 vs. 2.5+/-0.3 pg/ml, P<0.001) and TNF-alpha (2.7+/-0.2 vs. 3.8+/-0.2 pg/ml, P<0.01) were elevated in CHF. LogIL-6 and logTNF-alpha were positively correlated (r=0.34 and r=0.35, respectively) with logplasma norepinephrine, and were negatively correlated (r=-0.39 and r=-0.32, respectively) with peak VO(2). Maximal exercise increased IL-6 and TNF-alpha both in controls and CHF (all P<0.01). Changes in IL-6 (DeltaIL-6) correlated with Deltaepinephrine (r=0.63, P<0.0001) and Deltanorepinephrine (r=0.57, P=0.0006) in controls, but not in CHF. DeltaTNF-alpha correlated with DeltaANP (r=0.28, P=0.01) only in CHF. In summary, cytokine activation at rest was associated with high plasma norepinephrine and exercise intolerance. Maximal exercise caused increases in IL-6 and TNF-alpha concentrations. Sympathetic activation seems to be important for the IL-6 increase during exercise in controls. In CHF, changes in ANP during exercise were associated with the exercise-induced increase in TNF-alpha, but still unknown mechanisms are involved for the cytokine activation during exercise.     

Activated monocytes and platelet‐monocyte aggregates in patients with sickle cell disease*

Tumour necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) increase endothelial surface receptors that mediate the adherence of sickle erythrocytes to the endothelium. Increased circulating levels of these cytokines have been found in patients with sickle cell disease (SCD). Monocytes are a source of both of these inflammatory mediators; we therefore determined whether circulating monocytes were activated in SCD, as defined by intracellular expression of these cytokines. Blood was also assayed for the presence of platelet–monocyte aggregates (PMAs), as platelet adherence is one possible mechanism for monocyte activation. The median percentages of monocytes expressing intracellular TNF‐α and IL‐1β in SCD patients were 6.8 (2.8–17.3) [median (range)] and 14.1 (1.3–44.8), respectively. In African‐American controls the corresponding percentages were 0.3 (0.1–0.5) and 0.4 (0.1–3.0), and in Caucasians 0.2 (0.1–0.5) and 0.8 (0.8–1.9) (P < 0.001, Kruskal–Wallis). The mean percentage (± SD) of PMA was 14.0 ± 8.3 for Caucasian controls, 25.7 ± 7.3 for African‐American controls, and 45.7 ± 21.6 for patients with SCD (P < 0.001, RM ANOVA; P < 0.05, Newman–Keuls posthoc test). We conclude that there are increased circulating PMAs and monocyte activation in patients with SCD.     

Increased expression of tumor necrosis factor-alpha converting enzyme and tumor necrosis factor-alpha in peripheral blood mononuclear cells in patients with advanced congestive heart failure

BACKGROUND: Tumor necrosis factor-alpha converting enzyme (TACE) has recently been identified as a metalloproteinase-disintegrin, which converts pro-tumor necrosis factor-alpha (TNF-alpha) to the mature form, and is an important mediator in the pathogenesis of CHF. AIMS: In order to establish the importance of TACE in the regulation of TNF-alpha synthesis in peripheral blood mononuclear cells (PBMC), we analyzed mRNAs and protein-positive cells of both TACE and TNF-alpha in PBMC obtained from patients with congestive heart failure (CHF). METHODS AND RESULTS: PBMC were obtained from 46 patients with CHF and 22 controls. PBMC were activated by phorbol 12-myristate 13-acetate and ionomycin and assessed for TACE and TNF-alpha mRNAs by real-time RT-PCR, intracellular TACE and TNF-alpha levels by flow cytometry, and TNF-alpha secretion by supernatant ELISA. Levels of TACE and TNF-alpha mRNAs, intracellular TACE and TNF-alpha, and supernatant TNF-alpha were higher in CHF than in controls (P<0.001). There was a positive correlation between TACE and TNF-alpha levels in CHF patients (mRNA: r=0.60, P<0.001, intracellular protein levels: r=0.76, P<0.001). When the CHF group was divided into two subgroups by NYHA functional class (I and II vs. III and IV), levels of TACE and TNF-alpha were significantly higher in severe CHF patients (NYHA III or IV) than in mild CHF patients (NYHA I or II) (mRNA: P<0.001; intracellular protein levels: P<0.001). CONCLUSION: These results demonstrate that in patients with CHF, and especially those with severe CHF, TACE expression in PBMC increases with TNF-alpha expression. These observations suggest that TACE in PBMC is an important regulator of TNF-alpha maturation, meaning that TACE may be a potential target for the inhibition of cellular TNF-alpha production in CHF.     

Proinflammatory cytokine activation is linked to apoptotic mediator, soluble Fas level in patients with chronic heart failure

The Fas/Fas Ligand system is a major apoptosis signaling pathway that is up-regulated in patients with chronic heart failure (CHF). Serum soluble Fas (sFas) levels increase in proportion to the CHF severity and may have prognostic value, therefore, sFas is a promising biomarker of heart failure. In this study, we attempted to identify the determinants of sFas levels in patients with CHF. Serum levels of tumor necrosis factor (TNF)-α and its soluble receptors (sTNF-R1 & sTNF-R2), interleukin (IL)-6, soluble IL-6 receptor (sIL-6R), glycoprotein (gp)130, and sFas were measured in 106 patients with CHF and 39 controls. All subjects performed a symptom-limited cycle ergometer exercise test with expired gas analysis. CHF patients had higher levels of TNF-α, sTNF-R1, sTNF-R2, IL-6, and gp130. Serum levels of sFas (controls versus CHF; 2.60 ± 0.88 versus 3.38 ± 1.23 ng/mL, P = 0.0004) were higher in CHF. On univariate analysis, age (P = 0.0003), NYHA functional class (P = 0.0012), peak VO2 (P < 0.0001), plasma norepinephrine (P = 0.0013), log IL-6 (P < 0.0001), log TNF-α (P = 0.0002), log sTNF-R1 (P < 0.0001), and log TNF-R2 (P < 0.0001) were significantly related to log sFas levels. Multivariate analysis showed that age and log IL-6 and log sTNF-R1 levels were independently associated with log sFas levels (overall R = 0.603, P < 0.0001). Serum levels of sFas were increased in patients with CHF, and age and serum IL-6 and sTNF-R1 levels were independent determinants of sFas levels. These data suggest that proinflammatory cytokine activation is linked to the Fas/Fas Ligand system in patients with CHF.     

Association of interleukin‐18 expression with enhanced levels of both interleukin‐1β and tumor necrosis factor α in knee synovial tissue of patients with rheumatoid arthritis

Objective

To examine the expression patterns of interkeukin‐18 (IL‐18) in synovial biopsy tissue of patients with rheumatoid arthritis (RA), and to determine whether expression of this primary cytokine is related to the expression of other cytokines and adhesion molecules and related to the degree of joint inflammation.

Methods

Biopsy specimens of knee synovial tissue either without synovitis (n = 6) or with moderate or severe synovitis (n = 11 and n = 12, respectively) were obtained from 29 patients with active RA. Paraffin‐embedded, snap‐frozen sections were used for immunohistochemical detection of IL‐18, tumor necrosis factor α (TNFα), IL‐1β, IL‐12, and IL‐17. Furthermore, adhesion molecules, such as intercellular adhesion molecule 1, vascular cell adhesion molecule 1, and E‐selectin, and cell markers CD3, CD14, and CD68 were stained.

Results

IL‐18 staining was detectable in 80% of the RA patients, in both the lining and sublining of the knee synovial tissue. IL‐18 expression in the synovial tissue was strongly correlated with the expression of IL‐1β (in the sublining r = 0.72, in the lining r = 0.71; both P < 0.0001) and TNFα (in the sublining r = 0.59, P < 0.0007, and in the lining r = 0.68, P < 0.0001). In addition, IL‐18 expression in the sublining correlated with macrophage infiltration (r = 0.64, P < 0.0007) and microscopic inflammation scores (r = 0.78, P < 0.0001), and with the acute‐phase reaction as measured by the erythrocyte sedimentation rate (r = 0.61, P < 0.0004). Interestingly, RA synovial tissue that coexpressed IL‐18 and IL‐12 demonstrated enhanced levels of the Th1‐associated cytokine IL‐17.

Conclusion

Our results show that expression of IL‐18 is associated with that of IL‐1β and TNFα and with local inflammation in the synovial tissue of patients with RA. In addition, synovial IL‐18 expression correlates with the acute‐phase response. These data indicate that IL‐18 is a primary proinflammatory cytokine in RA that drives the local production of IL‐1β and TNFα.

     

慢性心力衰竭患者炎性细胞因子的变化及作用

目的探讨致炎细胞因子白细胞介素1(IL-1)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、γ干扰素(IFN-γ)和抗炎细胞因子白细胞介素10(IL-10)在慢性心力衰竭发生发展中的变化及作用。方法入选心力衰竭患者150例和健康对照50名,采用酶联免疫吸附法检测血清IL-1、IL-6、IL-10、TNF-α和IFN-γ的水平。结果心力衰竭组患者血清IL-1、IL-6、IL-10、TNF-α和IFN-γ的水平显著高于对照组(P<0.05或P<0.01),且随着纽约心功能分级(NYHA)的增加而升高,并与左心室射血分数(LVEF)呈负相关(r=-0.586、-0.454、-0.521、-0.514、-0.502,均为P<0.01),与左心室舒张末容积(LVEDV)呈正相关(r=0.603、0.45、0.542、0.519、0.438,均为P<0.01);IL-1、IL-6、TNF-α、IFN-γ总和与IL-10的比值:NYHAⅢ级和Ⅳ级患者高于对照组(P<0.05或P<0.01),NYHAⅣ级患者高于Ⅲ级和Ⅱ级患者(P<0.05),NYHAⅢ级患者高于Ⅱ级患者(P<0.05),但NYHAⅡ级患者与对照组间差异无统计学意义(P>0.05);冠心病心力衰竭和扩张型心肌病心力衰竭患者的IL-1、IL-6、IL-10、TNF-α和IFN-γ水平比较,差异无统计学意义(P>0.05)。结论心力衰竭患者致炎细胞因子和抗炎细胞因子均增高,但抗炎因子增加相对不足,炎症反应随着心力衰竭程度加重而加重,与心功能状态有相关性,与病因无显著相关性,细胞因子在心力衰竭的发生发展中起着重要的作用。     

Clinical relevance of persistently elevated circulating cytokines (tumor necrosis factor α and interleukin‐6) in the long‐term followup of patients with giant cell arteritis

Objective

To assess the clinical relevance of increased circulating cytokines in patients with giant cell arteritis (GCA) after long‐term followup.

Methods

We performed a cross‐sectional evaluation of 54 patients with biopsy‐proven GCA prospectively followed for a median of 5.4 years (range 4–10.5 years). GCA‐related complications, vascular events, relapses, current prednisone dose, time required to achieve a maintenance prednisone dosage <10 mg/day, cumulated prednisone at that point, and adverse effects during followup were recorded. Serum interleukin‐6 (IL‐6) and tumor necrosis factor α (TNFα) were determined by immunoassay.

Results

All patients were in clinical remission. Both cytokines were significantly higher in patients than in controls (mean ± SD 21 ± 35 versus 5 ± 11 pg/ml; P < 0.001 for IL‐6 and mean ± SD 32 ± 14 versus 16 ± 9 pg/ml; P < 0.001 for TNFα). No differences were found in patients with or without GCA‐related complications or vascular events during followup. Circulating cytokines were significantly higher in patients who had experienced relapses (mean ± SD 25 ± 39 versus 10 ± 11 pg/ml; P = 0.04 for IL‐6 and mean ± SD 34 ± 15 versus 25 ± 11 pg/ml; P = 0.042 for TNFα). IL‐6 was significantly higher in patients still requiring prednisone (mean ± SD 29 ± 45 versus 13 ± 17 pg/ml; P = 0.008), and TNFα correlated with cumulated prednisone dose (r = 0.292, P = 0.04). No significant relationship was found between elevated cytokines and prednisone adverse effects or patients' quality of life.

Conclusion

Circulating TNFα and IL‐6 may persist elevated in GCA patients after long‐term followup and remain higher in patients who have experienced more relapsing disease. However, in this patient cohort, elevated circulating cytokines were not associated with increased frequency of GCA complications, vascular events, or treatment‐related side effects.     

The role of interleukin (IL)-17 in anxiety and depression of patients with rheumatoid arthritis

Background: Pro‐inflammatory cytokines are found to be elevated in patients with anxiety and depression but whether their serum levels are related to anxiety and depression is unknown. We used rheumatoid arthritis (RA) as an inflammatory disease model to explore such relationships. Methods: Eighteen RA patients and 18 healthy controls matched for age and gender were assessed for the severity of anxiety and depression with the hospital anxiety and depression scale (HADS). Disease activity of RA and pain were assessed by the Disease Activity Scale (DAS‐2)8 and visual analogue scale of pain, respectively. Serum pro‐inflammatory cytokine levels, including tumor necrosis factor (TNF)‐α, interleukin (IL)‐6 and IL‐17 were determined by enzyme‐linked immunosorbant assay. The differences in cytokine levels between RA patients and healthy controls, as well as within the RA group with and without anxiety and depression, were compared by using the Mann–Whitney U‐test. The correlations between anxiety, depression and pro‐inflammatory cytokines were explored by Spearman’s rank correlation. Multiple linear regression was used to adjust for DAS‐28 and pain. Results: Serum TNF‐α, IL‐6 and IL‐17 levels were significantly higher in RA patients than those of healthy subjects (P < 0.001, P = 0.012 and P = 0.016, respectively). Within the RA group, serum IL‐17 level was significantly higher in those with anxiety than those without (P = 0.044). Additionally, IL‐17 level was positively correlated with the severity of anxiety, even after adjustment for DAS‐28 and pain. Conclusion: Serum IL‐17 was elevated in RA patients, especially in those with anxiety. In addition, IL‐17 level was independently associated with higher anxiety score.