神经梅毒患者血清白细胞介素-4干扰素-γ的变化及其临床意义

2014-08-07 10:30吕远  周静
中国医药科学 2014年9期
关键词:介素脑脊液梅毒

吕远  周静

[摘要] 目的 探讨神经梅毒患者血清白细胞介素-4(IL-4)、干扰素-γ(IFN-γ)的变化及其临床意义。 方法 选取2007年1月~2013年10月期间我院诊治的神经梅毒患者34例(神经梅毒组)及非神经梅毒患者34例(非神经梅毒组),选取34例正常体检者为对照组,患者在入院后及治疗1个月后、体检者在体检结束未发现有异常疾病后抽血检测IL-4、IFN-γ。 结果 三组之间IL-4、IFN-γ浓度明显存在不同(P<0.05),神经梅毒组、非神经梅毒组IL-4、IFN-γ浓度高于对照组(P<0.05),神经梅毒组与非神经梅毒组IL-4、IFN-γ浓度比较差异无统计学意义(P>0.05),神经梅毒组患者在治疗后IL-4、IFN-γ浓度明显低于治疗前(P<0.05)。 结论 神经梅毒与非神经梅毒患者均存在IL-4、IFN-γ升高变化,神经梅毒与非神经梅毒患者之间IL-4、IFN-γ无明显差异,经过治疗IL-4、IFN-γ水平会明显下降。

[关键词] 神经梅毒;白细胞介素-4;干扰素-γ

[中图分类号] R759.1   [文献标识码] A   [文章编号] 2095-0616(2014)09-22-04

Changes of serum interleukin-4 and IFN-γ in patients with neurosyphilis and their clinical significance

LV Yuan1  ZHOU Jing2

1.Department of Comprehensive Medicine, Shanwei Yihui Foundation Hospital, Shanwei 516600,China; 2.Department of Dermatology, Shanwei Yihui Foundation Hospital, Shanwei 516600,China

[Abstract] Objective To investigate the changes of serum interleukin-4(IL-4) and interferon-γ(IFN-γ) in the patients with neurosyphilis and their clinical significance. Methods Thirty-four patients with neurosyphilis(neurosyphilis group) and 34 patients with non-neurosyphilis(non-neurosyphilis group) treated in our hospital from January 2007 to October 2013 were selected, and 34 normal health examinees were selected as the control group. The patients blood was drawn to examine the IL-4 and IFN-γ after admission, 1 month after treatment and when not discovering abnormal diseases at the end of health examination. Results The three groups were significantly different in the IL-4 and IFN-γ concentrations(P<0.05); The neurosyphilis group and the non-neurosyphilis group had higher IL-4 and IFN-γ concentrations than the control group(P<0.05); The neurosyphilis group and the non-neurosyphilis group were not different in the IL-4 and IFN-γ concentrations, with no statistical significance(P>0.05); The IL-4 and IFN-γ concentrations of the neurosyphilis group after treatment were significantly lower than those before treatment(P<0.05). Conclusion Both the neurosyphilis group and the non-neurosyphilis group have elevated IL-4 and IFN-γ concentrations; The neurosyphilis group and the non-neurosyphilis group were not significantly different in the IL-4 and IFN-γ; The IL-4 and IFN-γ levels decrease significantly after treatment.

[Key words] Neurosyphilis; Interleukin-4; Interferon-γ

梅毒为梅毒螺旋体(treponema pallidum, TP)感染所致的一种慢性的性传播疾病,患者根据病情发展阶段也分为潜伏期梅毒、一期梅毒、二期梅毒、三期梅毒、先天性梅毒[1],如患者临床症状累及到神经系统则称为神经梅毒,患者可出现头痛、呕吐、偏瘫等神经系统受累症状[2]。研究发现梅毒患者其细胞免疫存在异常变化可能是导致梅毒发病的关键

环节[3],干扰素-γ(IFN-γ)、白细胞介素-4(IL-4)均是与T细胞免疫相关因子[4-5],因此笔者对我院收治的神经梅毒患者血清IFN-γ、IL-4进行了检测,从而探讨神经梅毒患者血清白细胞介素-4、干扰素-γ的变化及其临床意义,现将结果报道如下。

1 资料与方法

1.1 一般资料

选取我院2007年1月~2013年10月期间诊治的神经梅毒患者34例(神经梅毒组)及非神经梅毒患者34例(非神经梅毒组),入选标准:(1)患者均通过RRP实验初筛诊断为梅毒,行TPPA试验阳性确诊。(2)在我院诊治前1个月内未接受过任何免疫调节剂、糖皮质激素、抗菌药物治疗。(3)神经梅毒患者有头痛、面瘫等神经系统症状而排除其他原因所致者,同时脑脊液检查显示淋巴细胞及蛋白升高、脑脊液TPPA试验阳性。排除标准:(1)伴有其他性传播疾病者。(2)妊娠期及哺乳期妇女。(3)神经系统症状为周围神经炎、脑血管病、脑炎等其他神经系统疾病所致者。神经梅毒组入选患者其中男21例,女13例,年龄26~43岁,平均(36.3±5.5)岁,病程3~12年,平均(6.87±2.31)年;根据患者病情分期Ⅰ期梅毒12例,Ⅱ期梅毒10例,Ⅲ期梅毒2例;根据神经系统累及部位不同分为:脑膜神经梅毒3例、血管神经梅毒15例、脊髓痨神经梅毒2例、其他神经梅毒4例。

endprint

非神经梅毒组患者,其中男24例,女10例,年龄22~41岁,平均(35.2±5.4)岁,病程2~11年,平均(6.46±2.28)年;根据患者病情分期Ⅰ期梅毒15例,Ⅱ期梅毒8例,Ⅲ期梅毒1例。以收治1例神经梅毒患者的同时随机选取门诊行健康体检的正常人1例原则,选取34例正常体检者为对照组,均行RRP及TPPA试验排除梅毒,近1个月内未接受过任何免疫调节剂、糖皮质激素、抗菌药物治疗史,其中男19例,女15例,年龄18~46岁,平均(35.0±6.5)岁。三组在年龄、性别方面比较差异无统计学意义(P>0.05),神经梅毒与非神经梅毒组患者在梅毒分期方面比较差异无统计学意义(P>0.05),入选对象均知情同意。

1.2 方法

患者在入院后及治疗1个月后、体检者在体检结束未发现有异常疾病后,采集外周静脉血2mL,置于无菌真空试管内静置15min后放在离心机内以3000r/min转速离心处理20min,静置30min待血清分层,取得血清(上清液)后以ELISA法检测IL-4、IFN-γ,IL-4、IFN-γ检测试剂盒购自深圳晶美生物工程有限公司,所有操作严格按照试剂盒说明检测。

1.3 统计学方法

采用SPSS17.0统计学软件进行统计分析,计量资料两组检验采用t检验,多组检验采用方差分析,P<0.05为差异具有统计学意义。

2 结果

2.1 各组IL-4、IFN-γ检测结果比较

神经梅毒组、非神经梅毒组、对照组三组之间IL-4、IFN-γ明显存在不同(P<0.05),其中神经梅毒组、非神经梅毒组IL-4、IFN-γ浓度高于对照组(P<0.05),神经梅毒组与非神经梅毒组IL-4、IFN-γ浓度比较差异无统计学意义(P>0.05),见表1。

表1  各组IL-4、IFN-γ检测结果比较(,ng/L)

组别 n IL-4 IFN-γ

神经梅毒组 34 140.71±50.04 213.76±20.06

非神经梅毒组 34 134.03±43.23 206.37±13.65

对照组 34 34.82±13.48 160.24±14.63

F 19.63 6.74

P <0.05 <0.05

注:与对照组比较,P<0.05,其中神经梅毒组IL-4 t=11.91、IFN-γ t=12.78,非神经梅毒组,IL-4 t=12.57、IFN-γ t=13.44

2.2 神经梅毒组患者治疗前后IL-4、IFN-γ检测结果比较

神经梅毒组患者在治疗后IL-4、IFN-γ浓度明显低于治疗前,治疗前后比较差异具有统计学意义(P<0.05),见表2。

表2  神经梅毒组患者治疗前后IL-4、IFN-γ检测结果比较

(,ng/L)

组别 n IL-4 IFN-γ

治疗前 34 140.71±50.04 243.76±20.06

治疗后 34 110.73±43.21 213.08±14.55

t 2.64 7.22

P <0.05 <0.05

3 讨论

神经梅毒是梅毒中较为严重的一种特殊类型,神经梅毒主要分为无症状性神经梅毒、脑膜神经梅毒、血管神经梅毒、脊髓痨神经梅毒、麻痹性神经梅毒、先天性神经梅毒,其中无症状梅毒无明显症状,临床发现的神经梅毒多为血管神经梅毒及脑膜神经梅毒[6-8],患者以周围神经炎等症状出现而就诊,检测脑脊液TPPA阳性可确诊。

研究发现梅毒的发病与梅毒螺旋体入侵导致人体免疫功能发生异常变化有关[3],在梅毒螺旋体感染人体后,机体反应性的发生免疫应答反应,主要表现为巨噬细胞及T细胞的活性增强,此时IFN-γ及白细胞介素会大量分泌。IFN-γ主要有Th1细胞产生,能上调白细胞介素-12的分泌增强,反过来白细胞介素-12又能促使NK细胞分泌INF-γ,IL-4主要为Th2细胞产生,能对细胞免疫功能进行抑制,对Th2细胞具有促使分化定向的作用,因而IL-4、INF-γ的异常往往提示机体免疫功能的异常[3]。临床研究证实早期梅毒患者INF-γ、IL-12等明显升高[9-10],在免疫应答状态下表现为Th1的优势明显,因而能起到清除梅毒螺旋体的作用,随着病情控制INF-γ、IL-4会有所下降,在患者病情进入II期梅毒后,患者的INF-γ、IL-4会明显呈现下降趋势,此时表现为Th2免疫反应的优势较强,但是对神经梅毒患者INF-γ、IL-4的变化临床研究相对较少,Logo EC、Gnanasgaram M、Schotanus M等[11-13]国外学者研究发现神经梅毒患者与普通梅毒患者一样均出现Th1/Th2的免疫漂移,INF-γ、IL-4在梅毒患者血清中有升高变化。本文对神经梅毒与非神经梅毒患者INF-γ、IL-4变化进行了对照研究,结果显示神经梅毒患者INF-γ、IL-4水平与非神经梅毒患者之间并无明显不同,提示梅毒螺旋体的感染繁殖数量与病情进程可能无关,病情的进展是由于Th1/Th2免疫应答平衡发生改变所致,而无论是神经梅毒还是非神经梅毒患者均较正常人群均表现为INF-γ、IL-4水平升高。本文对神经梅毒患者治疗前后的INF-γ、IL-4水平变化进行了观察,结果显示在有效治疗后患者INF-γ、IL-4水平明显较治疗前下降,提示有效的治疗也改善患者的Th1/Th2失衡情况,与国内外相关研究报道结果相符[14-18]。有报道显示早期梅毒患者INF-γ呈现高水平表达[2],在随着患者分期的进展有降低,认为免疫应答过程中Th1优势变化逐渐转变为Th2优势变化,免疫水平处于不断降低过程,因而预后较差,由于神经梅毒患者临床少见,因而本研究未能就患者所处分期情况进一步研究是否存在INF-γ、IL-4水平的不同表达。

综上所述,神经梅毒与非神经梅毒患者均存在IL-4、IFN-γ升高变化,神经梅毒与非神经梅毒患者之间IL-4、IFN-γ无明显差异,经过治疗IL-4、IFN-γ水平会明显下降。

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[6] 谭燕,王丽娟,张玉虎,等.神经梅毒脑脊液蛋白含量与3年远期预后相关研究[J].中华神经医学杂志,2013,12(2):183-186.

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[8] Kinson RM,Chan LG.Psychiatric Symptoms as the Sole Manifestation of Neurosyphilis[J].The Journal of neuropsychiatry and clinical neurosciences,2013,25(4):E39-E40.

[9] 刘春,齐淑贞,龙福泉,等.梅毒患者白介素4和Toll样受体2基因单核苷酸动态性研究[J].国际皮肤性病学杂志,2010,26(6):306-308.

[10] 王瑞,曹鸿玮,郑晓红,等.血清干扰素γ、白细胞介素18在早期梅毒的表达及临床意义[J].中华医院感染学杂志,2013,23(16):3830-3832.

[11] Lago EG,Vaccari A,Fiori RM.Clinical features and follow-up of congenital syphilis[J].Sexually transmitted diseases,2013,40(2):85-94.

[12] Gnanasegaram M,Coutts I.A case of adrenal insufficiency secondary to syphilis and difficulties in the diagnostic work‐up[J].Australasian Journal of Dermatology,2013,54(1):e19-e21.

[13] Schotanus M,Dorleijn DMJ,Hosman AJF,et al.A patient with multifocal tabetic arthropathy: a case report and review of literature[J].Sexually transmitted diseases,2013,40(3):251-257.

[14] Pastuszczak M,Jakiela B,Wielowieyska-Szybinska D,et al.Elevated cerebrospinal fluid interleukin-17A and interferon-[gamma] levels in early asymptomatic neurosyphilis[J].Sexually transmitted diseases,2013,40(10):808-812.

(下转第页)

(上接第页)

[15] Patel VB,Singh R,Connolly C,et al.Comparative utility of cytokine levels and quantitative RD-1-specific T cell responses for rapid immunodiagnosis of tuberculous meningitis[J].Journal of clinical microbiology,2011,49(11):3971-3976.

[16] Bijker EM,Bastiaens GJH,Teirlinck AC,et al.Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity[J].Proceedings of the National Academy of Sciences,2013,110(19):7862-7867.

[17] 师金川,季必华,常小丽,等.梅毒血清复发患者脑脊液IFN-γ等指标检测结果分析[J].中国艾滋病性病,2013(3):195-197.

[18] 丁岩,刘平.神经梅毒的诊治研究进展[J].中国老年学杂志,2011,31(16):3214-3216.

(收稿日期:2014-03-13)

endprint

[6] 谭燕,王丽娟,张玉虎,等.神经梅毒脑脊液蛋白含量与3年远期预后相关研究[J].中华神经医学杂志,2013,12(2):183-186.

[7] Liu LL,Zheng WH,Tong ML,et al.Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients[J].Journal of the neurological sciences,2012,317(1):35-39.

[8] Kinson RM,Chan LG.Psychiatric Symptoms as the Sole Manifestation of Neurosyphilis[J].The Journal of neuropsychiatry and clinical neurosciences,2013,25(4):E39-E40.

[9] 刘春,齐淑贞,龙福泉,等.梅毒患者白介素4和Toll样受体2基因单核苷酸动态性研究[J].国际皮肤性病学杂志,2010,26(6):306-308.

[10] 王瑞,曹鸿玮,郑晓红,等.血清干扰素γ、白细胞介素18在早期梅毒的表达及临床意义[J].中华医院感染学杂志,2013,23(16):3830-3832.

[11] Lago EG,Vaccari A,Fiori RM.Clinical features and follow-up of congenital syphilis[J].Sexually transmitted diseases,2013,40(2):85-94.

[12] Gnanasegaram M,Coutts I.A case of adrenal insufficiency secondary to syphilis and difficulties in the diagnostic work‐up[J].Australasian Journal of Dermatology,2013,54(1):e19-e21.

[13] Schotanus M,Dorleijn DMJ,Hosman AJF,et al.A patient with multifocal tabetic arthropathy: a case report and review of literature[J].Sexually transmitted diseases,2013,40(3):251-257.

[14] Pastuszczak M,Jakiela B,Wielowieyska-Szybinska D,et al.Elevated cerebrospinal fluid interleukin-17A and interferon-[gamma] levels in early asymptomatic neurosyphilis[J].Sexually transmitted diseases,2013,40(10):808-812.

(下转第页)

(上接第页)

[15] Patel VB,Singh R,Connolly C,et al.Comparative utility of cytokine levels and quantitative RD-1-specific T cell responses for rapid immunodiagnosis of tuberculous meningitis[J].Journal of clinical microbiology,2011,49(11):3971-3976.

[16] Bijker EM,Bastiaens GJH,Teirlinck AC,et al.Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity[J].Proceedings of the National Academy of Sciences,2013,110(19):7862-7867.

[17] 师金川,季必华,常小丽,等.梅毒血清复发患者脑脊液IFN-γ等指标检测结果分析[J].中国艾滋病性病,2013(3):195-197.

[18] 丁岩,刘平.神经梅毒的诊治研究进展[J].中国老年学杂志,2011,31(16):3214-3216.

(收稿日期:2014-03-13)

endprint

[6] 谭燕,王丽娟,张玉虎,等.神经梅毒脑脊液蛋白含量与3年远期预后相关研究[J].中华神经医学杂志,2013,12(2):183-186.

[7] Liu LL,Zheng WH,Tong ML,et al.Ischemic stroke as a primary symptom of neurosyphilis among HIV-negative emergency patients[J].Journal of the neurological sciences,2012,317(1):35-39.

[8] Kinson RM,Chan LG.Psychiatric Symptoms as the Sole Manifestation of Neurosyphilis[J].The Journal of neuropsychiatry and clinical neurosciences,2013,25(4):E39-E40.

[9] 刘春,齐淑贞,龙福泉,等.梅毒患者白介素4和Toll样受体2基因单核苷酸动态性研究[J].国际皮肤性病学杂志,2010,26(6):306-308.

[10] 王瑞,曹鸿玮,郑晓红,等.血清干扰素γ、白细胞介素18在早期梅毒的表达及临床意义[J].中华医院感染学杂志,2013,23(16):3830-3832.

[11] Lago EG,Vaccari A,Fiori RM.Clinical features and follow-up of congenital syphilis[J].Sexually transmitted diseases,2013,40(2):85-94.

[12] Gnanasegaram M,Coutts I.A case of adrenal insufficiency secondary to syphilis and difficulties in the diagnostic work‐up[J].Australasian Journal of Dermatology,2013,54(1):e19-e21.

[13] Schotanus M,Dorleijn DMJ,Hosman AJF,et al.A patient with multifocal tabetic arthropathy: a case report and review of literature[J].Sexually transmitted diseases,2013,40(3):251-257.

[14] Pastuszczak M,Jakiela B,Wielowieyska-Szybinska D,et al.Elevated cerebrospinal fluid interleukin-17A and interferon-[gamma] levels in early asymptomatic neurosyphilis[J].Sexually transmitted diseases,2013,40(10):808-812.

(下转第页)

(上接第页)

[15] Patel VB,Singh R,Connolly C,et al.Comparative utility of cytokine levels and quantitative RD-1-specific T cell responses for rapid immunodiagnosis of tuberculous meningitis[J].Journal of clinical microbiology,2011,49(11):3971-3976.

[16] Bijker EM,Bastiaens GJH,Teirlinck AC,et al.Protection against malaria after immunization by chloroquine prophylaxis and sporozoites is mediated by preerythrocytic immunity[J].Proceedings of the National Academy of Sciences,2013,110(19):7862-7867.

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[18] 丁岩,刘平.神经梅毒的诊治研究进展[J].中国老年学杂志,2011,31(16):3214-3216.

(收稿日期:2014-03-13)

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