Alzheimer病病人血清与脑脊液白细胞介素-1及肿瘤坏死因子水平检测的研究

目的　为探讨炎性细胞因子 (CK)在Alzheimer病 (AD)慢性炎性病理过程中的作用。方法　本研究采用ELISA法对AD病人 (1 1例 )、血管性痴呆 (VD)病人 (1 3例 )与正常对照 (1 3名 )的血清与脑脊液 (CSF)、白细胞介素 1 β(IL 1 β)和肿瘤坏死因子 (TNF α)的水平进行了测定。 结果　与VD(38 51± 1 4 39)pg/ml、正常对照 (33 98± 1 6 31 )pg/ml相比 ,AD病人血清IL 1 β水平 (60 1 3± 1 7 81 )pg/ml明显升高 ,P <0 0 1。AD病人血清TNF α水平 (81 2 0± 2 3 99)pg/ml虽较VD(71 77± 2 8 86)pg/ml和正常对照 (73 91± 1 7 69)pg/ml轻度升高 ,但并无统计学意义。AD病人CSFIL 1 β水平 (38 2 5±1 8 42 )pg/ml明显高于对照组 (2 0 2 5± 1 5 86 )pg/ml和VD病人 (32 1 8± 1 9 81 )pg/ml,P <0 0 5。AD病人CSFTNF α水平 (1 4 2 58± 1 1 46)pg/ml也明显高于VD病人 (1 1 5 46± 1 9 52 )pg/ml,P <0 0 5 )和对照组 (1 0 6 2 3± 2 6 1 3)pg/ml,P <0 0 1。结论　上述结果表明 ,炎性细胞因子IL 1 β和TNF α在AD的神经变性过程起着重要的作用 ,炎症可参与AD的发病机制。开发针对AD细胞因子网络的特异性治疗有着相当意义     

老年性痴呆患者血清叶酸和维生素B12的临床观察

目的　了解老年性痴呆患者叶酸和维生素B12 水平 ,并探讨二者与痴呆的关系。方法　研究对象为 6 0岁以上的老年人 10 4例 ,患有老年性痴呆者 76例 ,其中老年性痴呆 (AD) 33例 ,血管性痴呆 (VD) 4 3例 ,健康老年者 2 8人作为对照组。对所有研究对象进行临床病史询问、内科和神经科查体 ,空腹取血检测血清叶酸和维生素B12 。结果　老年性痴呆患者叶酸的平均水平为 (7.6 5± 2 .4 8)ug/L(AD)和 (8.5 4± 3.34)ug/L(VD) ,维生素B12 的平均水平为 (312 .4 3± 182 .5 )ng/L(AD)和 (713.5 8± 6 2 5 .94 )ng/L(VD) ,对照组叶酸和VitB12 的平均水平分别为 (11.35± 3.76 )ug/L和 (5 0 7.8± 4 5 2 .85 )ng/L ,分别与对照组比较有显著性差异 (P <0 .0 5 )。结论　老年性痴呆者与血清低叶酸水平有关 ,而与低维生素B12 水平无关。     

重症肌无力患者血清可溶性白细胞介素—2受体的研究

应用酶联免疫吸附法 ( ELISA)测定 4 7例重症肌无力 ( MG)患者和 2 2例健康对照者血清中可溶性白细胞介素 - 2受体 ( s IL- 2 R)水平 ,结果发现 MG患者血清 s IL- 2 R水平明显高于健康对照组 ( P<0 .0 0 5,P<0 .0 0 1) ,且各型之间亦具有显著性差异 ( P<0 .0 0 1)。病情越重 ,临床记分越高 ,s IL - 2 R水平越高 ;免疫抑制剂治疗后较治疗前明显下降 ,临床记分与 s IL - 2 R滴度呈正相关。认为对 MG患者血清 s IL -2 R的测定 ,有助于对该病进行动态观察 ,可作为判断病情的客观指标     

阿尔茨海默病和血管性痴呆患者脑脊液中乙酰胆碱和胆碱检测及其临床意义

目的　探讨阿尔茨海默病 (AD)和血管性痴呆 (VD)患者脑脊液 (CSF)中乙酰胆碱 (ACh)和胆碱 (Ch)含量的异同以及它们与认知障碍的关系。方法　采用简易精神状态量表 (MMSE)对 2 2例AD、2 2例VD和 2 0名对照进行认知功能评分 ,利用高效液相色谱 电化学检测方法 (HPLC ECD)进行CSF的ACh和Ch检测 ,而后进行比较和分析。结果　AD组患者CSF的ACh含量 [(10 .7± 5 .1)nmol/L]低于对照组 [(34 .5± 9.0 )nmol/L](P =0 .0 0 1) ,与MMSE评分呈正相关。VD组患者CSF的ACh含量 [(16 .8± 7.4)nmol/L]也低于对照组 (P =0 .0 0 1) ,与MMSE评分呈正相关。AD组的CSF中Ch含量与对照组相比 [分别为 (6 2 7.6± 145 .1)nmol/L和 (716 .0± 15 9.4)nmol/L],差异无显著意义 ,与MMSE不呈相关关系。VD组患者CSF的Ch含量 [(887.4± 187.4)nmol/L]高于对照组 (P =0 .0 0 2 )和AD组患者 (P =0 .0 0 1)。结论　 (1)ACh的降低与认知障碍呈正相关 ,提示ACh是与记忆有关的重要神经递质 ;(2 )VD的ACh降低提示有与AD类似的发病机制 ;(3)AD患者ACh显著降低和VD患者胆碱显著增高有助于两者之间的鉴别 ;(4 )应用胆碱酯酶抑制剂来提高脑内ACh水平 ,不仅适用于AD ,也适用于VD。     

Alzheimer病患者血清和脑脊液中IL-6及sIL-6R水平的研究

目的　探讨Alzheimer病 (AD)患者血清和脑脊液 (CSF)中白细胞介素 6 (IL 6 )及白细胞介素 6受体 (sIL 6R)水平的变化。方法　采用双抗体夹心酶联免疫吸附试验 (ELISA)分别对 11例AD患者、13例血管性痴呆 (VD)患者及 13例正常对照者 (NC)血清和CSF中IL 6及sIL 6R水平进行了检测。结果　 (1)CSF中IL 6和sIL 6R水平各组检测的阳性率均较高 ,依次为AD >VD >NC ,痴呆两组与对照组比较均有显著性差异 (均P <0 .0 1)。 (2 )痴呆两组患者血清sIL 6R的阳性率明显高于对照组 (均P <0 .0 1)。 (3)CSF中IL 6和sIL 6R水平存在显著正相关 (r=0 .75 ,P <0 .0 5 ) ,与MMSE量表得分呈负相关 (r =- 0 .6 9,P <0 .0 5 )。结论　CSF中IL 6水平与痴呆严重程度有关 ,检测CSF中IL 6更能反映痴呆患者的免疫炎性改变 ,不仅为AD的慢性免疫炎症机制提供了理论依据 ,也将为AD的诊断和治疗提供新的途径     

广泛性焦虑患者单胺递质、神经内分泌及免疫的动态观察

目的　探讨广泛性焦虑患者于中国道家认知疗法治疗前后的血浆肾上腺素 (EPH)、去甲肾上腺素 (NE)、促肾上腺皮质激素 (ACTH)、皮质醇 (CS)和白细胞介素Ⅱ (IL 2 )水平的动态变化。方法　收集 2 9例患者接受中国道家认知疗法治疗 6个月 ,于治疗前后取血测定上述生化指标 ,选择2 9名年龄和性别相匹配的正常人作为对照组。结果　患者组治疗前EPH为 (5 91± 34 5 )ng/L、ACTH为 (2 4± 2 1)ng/L ,IL 2为 (2 2 3± 2 0 1)U/L ,均高于对照组 [(35 2± 10 9)ng/L、(12± 11)ng/L、(88± 86 )U/L],差异有显著性 (P <0 0 5 ) ;CS为 (79± 49)U/L ,低于对照组 (138± 74)U/L ,差异有显著性 (P <0 0 5 ) ;NE为 (741± 390 )ng/L ,与对照组 (75 1± 2 11)ng/L的差异无显著性 (P >0 0 5 )。患者经 6个月治疗焦虑症状缓解后 ,ACTH [(14± 9)ng/L]和IL 2 [(133± 76 )U/L]水平较治疗前降低 (P <0 0 5 ) ,CS[(148± 10 7)U/L]水平增高 (P <0 0 5 ) ,均接近于对照组水平 (P >0 0 5 )。结论　广泛性焦虑患者存在生化指标EPH、ACTH、CS和IL 2的异常 ,中国道家认知疗法可使患者的临床症状缓解、生化指标恢复正常。     

阿尔茨海默病患者血浆基质金属蛋白酶-3水平的对照研究

目的探讨阿尔茨海默病(AD)患者血浆基质金属蛋白酶-3(MMP-3)水平的变化。方法应用双抗体夹心酶联免疫法测定30例AD患者(AD组)、27例血管性痴呆(VD,VD组)患者及26名正常对照者(正常人组)的血浆MMP-3水平。根据简易精神状况检查量表(MMSE)评分将AD患者分为重度组(MMSE≤10分,8例)、中度组(MMSE>10分~≤20分,12例)和轻度组(MMSE>20分~<24分,10例)。血浆MMP-3水平采用方差分析进行统计学比较。结果AD组血浆MMP-3水平为(5.8±1.2)×104U/L,VD组为(5.3±0.8)×104U/L,正常人组为(4.8±0.8)×104U/L。AD组高于正常人组(P<0.001)及VD组(P<0.05),VD组亦高于正常人组(P<0.05)。AD重度组血浆MMP-3水平[(6.8±1.3)×104U/L]分别高于AD轻度组[(5.5±1.0)×104U/L]及AD中度组[(5.6±1.0)×104U/L],P均<0.05。AD组MMP-3水平与MMSE评分呈显著负相关(r=-0.450,P<0.05)。结论血浆MMP-3水平与AD严重程度相关;其水平增高可能与AD发病过程有关,其差异对AD与VD的鉴别可能有辅助价值。     

急性Guillain—Barre综合征患者血清sIL—2R和sIL—6R水平 …

目的　探讨可溶性白细胞介素 2受体 (s IL- 2 R)和可溶性白细胞介素 6受体 (s IL- 6 R)在急性Guillain- Barre综合征 (GBS)发病中的作用。方法　采用 EL ISA方法测定 32例 GBS患者和 30名正常对照者血清 s IL- 2 R及 s IL- 6 R水平。结果　 GBS患者血清 s IL- 2 R和 s IL- 6 R水平明显高于正常对照组 (P<0 .0 1,P<0 .0 5 ) ,重型和极重型患者明显高于轻型及中型患者 (P<0 .0 1,P<0 .0 5 ) ,且随着病情的好转 ,两种受体水平也逐渐下降 ,与治疗前比明显下降 (均 P<0 .0 5 )。结论　 s IL- 2 R和 s IL- 6 R水平的高低可作为判断 GBS病情变化的指标之一。     

载脂蛋白E、总补体与阿尔采默病的关系

目的　探讨载脂蛋白E(apoE)及总补体 (CH50 )与阿尔采默病 (AD)的关系。方法　应用自动化生化仪对 4 4例AD患者的apoE和总补体 (CH50 )进行测定 ,并与 2 9例血管性痴呆 (VD)患者进行对比。结果　AD组apoE为 (4.84± 3.10 )mg/dL ,高于VD组的 (4.2 1± 1.17)mg/dL ,差异有显著性 (t =1.6 7,P =0 .0 3) ;AD组CH50 为 (40 .5 2± 10 .1)ku/L ,低于VD组的 (45 .6 6± 9.9)ku/L ,差异有显著性 (t=1.6 7,P <0 .0 5 )。结论　载脂蛋白E异常是阿尔采默病发病的危险因素之一 ;载脂蛋白E的测定对鉴别阿尔采默病与血管性痴呆有一定价值 ;免疫反应在阿尔采默病中的作用不明     

白细胞介素-2及其受体在癫痫患者发作中的变化和对癫痫大鼠的致惊作用

目的探讨白细胞介素-2(interluekin-2, IL-2)及其可溶性受体在癫痫患者发作中的变化和对癫痫大鼠的致惊作用.方法采用ELISA方法检测58例癫痫患儿和23例健康儿血清IL-2及其可溶性受体的浓度,并进行分组比较;观察侧脑室注射IL-2对遗传性癫痫易感大鼠(P77PMC)惊厥发作的影响.结果癫痫组血清IL-2及其可溶性受体浓度[(25.86±5.21) ng/mL和(758.26±78.49) U/mL ]明显高于对照组[(13.78±3.24) ng/mL和(325.67±34.58) U/mL](P<0.01),且发作期[(30.31±6.77) ng/mL和(806.25±112.35) U/mL]高于间歇期[(20.27±4.66) ng/mL和(584.15±57.85) U/mL ](P<0.01),脑电图异常者[(27.18±4.35) ng/mL和(724.48±78.56) U/mL]高于正常者[(20.04±3.55) ng/mL和(621.85±77.45) U/mL],但与发作类型、病程长短及经治疗与否无关;侧脑室注射IL-2(5 000 U/L)5～10 μL后大鼠惊厥评分从26升高到36(P<0.05),惊厥持续时间从32 s延长到65 s(P<0.01),但对潜伏期无影响.结论 IL-2在癫痫患者处于高水平状态,直接侧脑室注射IL-2可加重大鼠惊厥程度,提示其参与癫痫发病过程.     

Soluble interleukin-1 receptor type II levels are elevated in cerebrospinal fluid in Alzheimer's disease patients

Evidence from epidemiological, clinical and experimental studies favour the hypothesis that inflammatory events are part of the neuropathology in Alzheimer's disease. Proinflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) have been found in activated microglia in the vicinity of amyloid plaques in Alzheimer's disease brain. In the present study, the levels of soluble IL-1 receptor type II (sIL-1R type II), IL-1 receptor antagonist (IL-1ra), IL-1beta, IL-6 and TNF-alpha were analyzed in cerebrospinal fluid (CSF) samples from Alzheimer's disease patients and control subjects. The levels of sIL-1R type II were significantly higher in CSF from Alzheimer's disease patients than in CSF samples from control subjects (38.5+/-8 pg/ml (mean+/-S.E.M.) vs. 7.9+/-4 pg/ml, p<0.05). Measurements of the proinflammatory cytokines IL-6 and TNF-alpha showed no significant difference between the two groups, and the levels of IL-1beta and IL-1ra in the present material were too low to permit detection. The increased levels of sIL-1R type II may reflect a compensatory mechanism to balance an increased release of IL-1 receptor agonists in the Alzheimer's disease brain.     

阿尔茨海默病患者外周血IL-6、IL-8、TNF-α水平与认知功能的相关性

目的 探讨阿尔茨海默病(AD)患者外周血白细胞介素-6(IL-6)、IL-8及肿瘤坏死因子α(TNF-α)水平与认知功能的相关性.方法 选择2015年1月~2016年1月在济宁医学院附属医院兖州院区治疗的AD患者90例作为研究组,并选择同期在我院体检的90名健康人作为对照组,采用酶联免疫吸附法(ELISA)检测两组研究对象的外周血IL-6、IL-8及TNF-α水平,并采用简易精神状态量表(MMSE)和临床痴呆评定量表(CDR)对其认知功能和日常行为能力进行评估.比较各组间炎性因子水平的差异,分析炎性因子表达水平与认知功能的相关性.结果 研究组AD患者外周血的IL-6、IL-8及TNF-α水平均明显高于对照组[(128.64±10.28)pg/ml比(103.59±8.72)pg/ml,(134.32±9.67)pg/ml比(101.45±7.32)pg/ml,(221.39±23.54)pg/ml比(109.68±18.76)pg/ml],差异均有统计学意义(P<0.05).受教育年限为AD患者认知功能的保护因素,IL-6、IL-8及TNF-α水平为危险因素(P<0.05).整体人群中IL-6、TNF-α水平与MMSE得分呈负相关(r=-0.314,-0.079;P<0.05),IL-8与MMSE无相关性.结论 外周血IL-6及TNF-α水平与轻度AD患者的认知功能相关.     

雷公藤多甙对格林-巴利综合征患者IL-6及其可溶性受体的影响

目的　探讨白细胞介素 (IL 6 )及其可溶性受体 (sIL 6R)在格林 巴利综合征 (GBS)发病中的作用及免疫抑制性药物对其影响。方法　按Asbury标准选择GBS患者 4 3例 ,并进行病情严重程度分级 (0～Ⅴ级 )。其中Ⅱ级 13例 ,Ⅲ级 2 3例 ,Ⅳ级 7例。按分层随机原则 ,将GBS者分为 2组 ,分别用肾上腺皮质类固醇 (激素 )和雷公藤多甙治疗 ,在开始前、治疗后第 8周各按统一标准进行评估 1次 ,并取静脉血和脑脊液 (CSF)配对标本 2mL ,用ELISA法测定sIL 6R和双抗体夹心ELISA法测定IL 6。结果　 (1)病初GBS者血清IL 6、sIL 6R分别为 (6 9.73± 2 5.2 5)ng/L和 (4 6 .6 5± 11.59) μg/L ,明显高于对照组的 (17.94± 5.6 6 )ng/L和 (2 9.2 5± 11.0 4 )μg/L(t =13.16 ,7.33,P <0 .0 0 1) ,此外CSFIL 6、sIL 6R分别为 (14.33± 6 .6 9)ng/L和 (9.4 5± 0 .98) μg/L ,亦明显高于对照组的 (3.35± 2 .79)ng/L和 (1.38± 0 .50 ) μg/L(t=10 .0 2 ,4 8.4 8,P <0 .0 0 1)。(2 )病初GBS者CSFIL 6、sIL 6R与病情严重程度分级相关密切 (r=0 .6 7,0 .4 8,P <0 .0 1)。(3)雷公藤多甙与激素治疗后两组临床症状均有不同程度的改善。但雷公藤多甙组临床严重程度分级进步 1级以上者为 90 .3% ,明显高于激素组的6 1.9% (x2 =5.0 6 ,P     

阿尔茨海默病患者血清IL-10和sIL-6R水平的变化

目的 探讨阿尔茨海默病(Alzheimer disease,AD)患者血清白细胞介素-10(interleukin-10,IL-10)、可溶性白细胞介素-6受体(soluble interleukin-6 receptor．sIL-6R)水平变化及其与痴呆严重程度的关系。方法 采用双抗体夹心ELISA法检测46例AD患者(AD组)、33名年龄匹配健康者(对照组)和40例脑梗死患者(CI组)血清IL-10、sIL-6R水平。结果 AD患者血清IL-10水平较正常对照组和CI组均明显降低，但对照组与CI组间差异无显著性。AD患者血清sIL-6R水平较正常对照组明显升高并随痴呆程度加重而不断上升；CI组中血清sIL-6R水平也明显高于对照组．但AD组和CI组间差异无显著性。结论 AD患者血清IL-10和sIL-6R水平的变化提示免疫炎性机制参与了AD的发病。     

Elevated interleukin-6 levels in cerebrospinal fluid of vascular dementia patients

OBJECTIVES: To investigate a possible implication of inflammatory processes in the development of dementia in cerebrovascular disease. PATIENTS AND METHODS: We examined the levels of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD) (n = 26), ischemic cerebrovascular disease without dementia (CVD) (n = 11), vascular dementia (VD) (n = 11), and other neurological disorders (n = 21) using sensitive enzyme-linked immunosorbent assay. RESULTS: The CSF concentrations of IL-6 were significantly elevated in patients with VD compared with those of patients with AD or CVD. CONCLUSION: The CSF IL-6 levels are increased in patients with VD, suggesting that inflammatory mechanisms may be involved in the development of cognitive decline in some patients with cerebrovascular disease. CSF IL-6 may be a biological marker for dementia in cerebrovascular disease.     

AD with subcortical white matter lesions and vascular dementia: CSF markers for differential diagnosis

We investigated whether the cerebrospinal fluid (CSF) biomarkers beta-amyloid 1-42 (Abeta1-42), total tau (t-tau) protein and tau protein phosphorylated at threonine 181 (p-tau181) could discriminate Alzheimer's disease (AD) from vascular dementia (VD) patients. CSF samples of Abeta1-42, t-tau, and p-tau181 were collected from probable AD (n=35), probable AD with white matter changes (WMC) indicative of concomitant cerebrovascular disorder (CVD, n=31), VD (n=20), and an age-matched subgroup of patients with other neurological disorders (OND) without cognitive impairment (n=24). AD patients showed very low Abeta1-42 levels (median=393 pg/ml). Abeta1-42, but not t-tau, differentiated AD from VD patients. However, the markers did not discriminate AD vs. AD plus WMC. In particular, both subgroups showed similar CSF biomarkers but they were significantly different from VD. ROC analysis showed that Abeta1-42 could discriminate AD from VD (AUC=0.85). The cutoff of 493 pg/ml gave sensitivity and specificity values of 77% and 80%, respectively. Similar results were obtained when Abeta1-42 was employed to discriminate AD with WMC from VD (95% specificity and 60% sensitivity, but with cutoff of 750 pg/ml). T-tau increased aspecifically in all cognitively impaired patients. P-tau181 performed better than t-tau in discriminating AD (with or without WMC) vs. VD. In conclusion, Abeta1-42 proved to be a valuable tool to discriminate AD vs. VD patients and possibly to improve diagnostic accuracy in clinical forms, improperly classified as "mixed dementia" based on radiological vascular lesions.     

Cerebrospinal fluid protein tau levels in the differential diagnosis of Alzheimer's disease

Tau protein concentration in cerebrospinal fluid was determined in 55 patients with Alzheimer's disease (AD), 18 patients with vascular dementia (VD), 19 patients with dementia caused by other disorders and 14 patients with major depression. Significantly (p < 0.05) elevated protein tau concentrations were found in AD patients (564.5 +/- 275.5 pg/ml) compared to all other patient groups (VD: 406.5 +/- 263.9 pg/ml; other dementia: 275.0 +/- 135.4 pg/ml; depression: 212.9 +/- 115.6 pg/ml). However, tau levels in AD patients covered a broad range (163.2 pg/ml-1200 pg/ml). AD patients with tau levels below the 25%-percentile of the distribution (among them a high percentage of patients with presenile onset) showed tau levels similar to those of the patients with late life depression. No significant correlations between tau levels and clinical variables such as severity of dementia, age, age of onset, duration of illness, and cerebral changes as assessed by volumetric magnetic resonance imaging could be demonstrated. Similarly, we could not find an influence of either APO-E genotype or psychotropic medication on the tau levels in AD patients. In accordance with other studies our results confirm elevated tau levels in AD compared to elderly not demented control subjects. Comparing groups, this finding applies as well with respect to VD and other dementing disorders. However, elevated tau levels cannot be detected in a subgroup of AD patients. This finding needs to be further investigated in future studies.     

Polymorphisms of the gene encoding the inflammatory cytokine interleukin-6 determine the magnitude of the increase in soluble interleukin-6 receptor levels in Alzheimer's disease. Results of a pilot study

Interleukin-6 (IL-6) is a multifunctional cytokine involved in the pathogenesis of Alzheimer's disease (AD). The effects of IL-6 are mediated through a specific receptor complex made up of a ligand binding glycoprotein (gp80 or IL-6R) and a signal transducing glycoprotein (gp130). Conflicting results have been reported concerning altered IL-6 or soluble IL-6R (sIL-6R) levels in serum and CSF in AD. This study investigated whether genetic heterogeneity determines the magnitude of the difference in IL-6 and sIL-6R levels in AD. Fifty-eight AD patients and 25 control subjects were included. Plasma and CSF IL-6 and sIL-6R levels were measured and the IL-6 variable number of number repeats ( IL-6vntr) and IL-6 promoter ( IL-6prom) genotypes were determined. sIL-6R levels in plasma and CSF were higher in AD patients than in control subjects. This elevation was striking among non-carriers of the IL-6vntr*C allele and among subjects homozygous for the IL-6prom*C allele whereas no difference in plasma and CSF sIL-6R levels was observed among carriers of the IL-6vntr*C allele and among subjects with the IL-6prom*CG and IL-6prom*GG genotypes. We conclude that plasma and CSF levels of sIL-6R are significantly increased in AD patients and that the magnitude of increase is determined by the IL-6 genotype.     

Th1 and Th2 serum cytokine profiles characterize patients with Hashimoto's thyroiditis (Th1) and Graves' disease (Th2)

OBJECTIVES: The aim of this study was to document the pattern of immune response, assessed by the measurement of both Th1 and Th2 serum cytokines, in patients suffering from autoimmune thyroid disease and toxic nodular goiter. METHODS: Both Th1 and Th2 serum cytokine levels were assayed in patients suffering from Graves' disease (GD, n = 25), Hashimoto's thyroiditis (HT, n = 21), and toxic nodular goiter (TNG, n = 7) and compared with corresponding levels of 25 healthy controls. Serum concentrations of IL-2, IL-1 beta, INF-gamma, TNF-alpha, IL-12, IL-15, IL-10, IL-18, IL-4 and IL-5 were assayed in fasting serum samples. RESULTS: It was found that patients with HT had higher IL-2 serum levels (12.16 +/- 0.66 pg/ml) compared to patients with TNG (9.25 +/- 0.84 pg/ml), GD (7.86 +/- 0.30 pg/ml) and controls (7.36 +/- 0.45 pg/ml; p = 0.0001), higher INF-gamma levels (7.60 +/- 0.33 pg/ml) compared to patients with TNG (5.77 +/- 0.55 pg/ml), GD (5.74 +/- 0.24 pg/ml) and controls (5.09 +/- 0.27 pg/ml; p = 0.0009), higher IL-12 levels (3.57 +/- 0.19 pg/ml) compared to patients with TNG (2.57 +/- 0.21 pg/ml), GD (2.48 +/- 0.13 pg/ml) and controls (2.59 +/- 0.23 pg/ml; p = 0.004), and higher IL-18 levels (27.52 +/- 1.75 pg/ml) compared to patients with TNG (18.71 +/- 2.24 pg/ml), GD (15.44 +/- 1.39 pg/ml) and controls (15.16 +/- 1.62 pg/ml; p = 0.0002). In contrast, patients with GD had higher serum levels of IL-4 (4.11 +/- 0.33 pg/ml) compared to patients with HT (3.0 +/- 0.16; p = 0.02) and higher IL-5 levels (4.22 +/- 0.30 pg/ml) compared to patients with TNG (3.21 +/- 0.58 pg/ml), HT (2.75 +/- 0.16 pg/ml) and controls (2.0 +/- 0.19 pg/ml; p = 0.0001). Patients had lower IL-1 beta serum levels (TNG 2.45 +/- 0.20, HT 2.52 +/- 0.14, GD 2.68 +/- 0.12 pg/ml) compared to controls (3.6 +/- 0.20 pg/ml; p = 0.008). CONCLUSIONS: The above findings suggest that a Th1 pattern of immune response characteristic of cellular immunity is dominant in HT, whereas the predominance of Th2 cytokines in GD indicates a humoral pattern of immune reaction.     

Influence of lithium treatment on GDNF serum and CSF concentrations in patients with early Alzheimer's disease

Preclinical and clinical studies gave evidence that lithium could be useful in the treatment of Alzheimer's disease (AD). One possible mechanism of action might be the induction of neurotrophins. Recently, we found a significant increase of brain-derived neurotrophic factor (BDNF) serum levels in AD patients treated with lithium and a significant decrease of ADAS Cog sum scores in comparison to placebo-treated patients. In another previous study we have shown that glial cell line-derived neurotrophic factor (GDNF) levels in CSF of patients with early AD are increased most probably due to an upregulated expression in CNS as an adaptive process of the impaired brain to enhance neurotrophic support at least in early stages of disease. Here we assessed the influence of a lithium treatment on GDNF serum and cerebrospinal fluid (CSF) concentrations in a subset of a greater sample recruited for a randomized, single-blinded, placebo-controlled, parallel-group multicenter 10-week study, investigating the efficacy of lithium treatment in AD patients. We found a significant negative correlation of lithium concentration in serum with GDNF concentration in CSF at the end of treatment (r = -0.585, p = 0.036) and with the difference of GDNF concentration in CSF before and after treatment (r = - 0.755, p = 0.003). However, we could not show a difference in GDNF concentrations between the patients after the treatment with lithium or placebo (serum, mean ± standard deviation: 434.3 ± 117.9 pg/ml versus 543.8 ± 250.0 pg/ml, p = 0.178; CSF, 62.3 ± 37.4 pg/ml versus 72.8 ± 43.9 pg/ml, p = 0.511). The findings of the present investigation indicated that beneficial effects of the lithium treatment might reduce the necessity of enhanced GDNF expression in the CNS in early AD.