慢性精神分裂症患者血清IL-2、IL-4和IL-10水平及与精神症状的相关性

目的探讨慢性精神分裂症患者血清白细胞介素2(IL-2)、白细胞介素4(IL-4)和白细胞介素10(IL-10)的水平变化及其与精神症状的相关性。方法于2012年12月-2013年10月在广州医科大学附属脑科医院采用抽签法选取符合《国际疾病分类(第10版)》(ICD-10)诊断标准的40例慢性精神分裂症住院患者为患者组,同期通过广告招募64例健康对照者为对照组。采用酶联免疫吸附试验(ELISA)检测两组血清IL-2、IL-4和IL-10水平,采用阳性和阴性症状量表(PANSS)评估患者组的精神症状。结果患者组血清IL-2水平高于对照组[(25.85±6.06)pg/m L vs.(12.63±1.90)pg/m L],差异有统计学意义(P0.05);两组血清IL-4水平[(7.36±1.54)pg/m L vs.(8.76±3.13)pg/m L]和IL-10水平[(4.29±0.87)pg/m L vs.(3.76±1.17)pg/m L]比较,差异均无统计学意义(P均0.05);患者组血清IL-2、IL-4和IL-10水平与病程、住院时长、抗精神病药治疗剂量及PANSS评分均无线性相关(P均0.05)。结论慢性精神分裂症患者的血清IL-2水平高于健康对照者,IL-4和IL-10水平与对照者比较未见差异;IL-2、IL-4和IL-10水平与患者的精神症状未见线性相关性。     

Low serum IL-10 concentrations and loss of regulatory association between IL-6 and IL-10 in adults with major depression

Elevated circulating pro-inflammatory cytokines are associated with symptoms of depression, and disorders involving chronic inflammation are often co-morbid with major depression. Since healthy immune regulation is accomplished through counter-balancing effects of pro- and anti-inflammatory cytokines, we hypothesized that depressed subjects (compared to controls) would express lower concentrations of the anti-inflammatory/immunoregulatory cytokine interleukin (IL)-10, and a higher IL-6/IL-10 ratio. We also examined the possibility that depressed subjects may exhibit a deficiency in the regulatory loop involving IL-6 induced secretion of IL-10. Therefore, we hypothesized that circulating IL-6 and IL-10 would be positively correlated in controls, while the correlation would be weaker in depressed subjects. Resting state serum cytokine concentrations were quantified in 12 unmedicated depressed subjects, and 11 age, gender, and ethnicity-matched controls. Depressed subjects showed significantly lower IL-10 (p = 0.03, Cohen’s d = −0.96), non-significantly higher IL-6, and significantly higher IL-6/IL-10 ratios (p = 0.05, Cohen’s d = 0.50). Across all participants, higher scores on the self-rated Inventory of Depressive Symptoms were associated with lower IL-10 (r(21) = −0.57, p = 0.005) and non-significantly higher IL-6/IL-10 ratios (r(21) = 0.38, p = 0.07), but not related to IL-6 concentrations. As hypothesized, IL-6 and IL-10 concentrations were strongly and positively correlated in controls (r(9) = 0.81, p = 0.003), but were completely dissociated in depressed subjects (r(10) = 0.01, p = 0.98). These results suggest that lower IL-10 levels, a higher IL-6/IL-10 ratio, and the apparent absence of a counter-balancing, immunoregulatory increase in IL-10 in response to elevated IL-6 concentrations contribute to the pro-inflammatory physiological milieu that is known to be associated with major depression. Therefore, reduced induction/availability of IL-10, that would normally inhibit pro-inflammatory cytokine actions and resolve inflammation, may contribute to the depressogenic as well as the inflammatory disease-promoting effects of chronic, low-level elevations in pro-inflammatory cytokines.     

难治性颞叶癫痫脑组织IL-6、IL-6受体及sIL-6R、 sgp130的表达及意义

目的 探讨IL-6、IL-6膜受体(IL-6R)及其下游信号转导相关分子在颞叶癫痫(TLE)发生中的作用. 方法 选择自2010年1月至2010年12月在第三军医大学新桥医院神经外科行手术治疗的TLE患者40例(TLE组),同期行手术治疗的外伤、高血压脑出血等患者40例(对照组);收集其手术过程中切除的颞叶组织.利用RT-PCR、ELISA等方法分析IL-6、IL-6R、sIL-6R以及sgp130的mRNA或蛋白水平的表达变化情况. 结果 TLE组和对照组中均可检测到IL-6和IL-6R mRNA的表达,但TLE组致病灶中IL-6和IL-6R mRNA水平均显著高于对照组,差异有统计学意义(P＜0.05).ELISA结果提示,sIL-6R在TLE组致痫灶中的表达量与对照组比较明显增高,差异有统计学意义(P＜0.05);sgpl30的含量略高于对照组,差异没有统计学意义(P＞0.05). 结论 局部高浓度的IL-6通过经典信号转导或者跨信号转导机制作用于TLE病灶细胞,影响这些细胞的生物学功能,参与癫痫发生过程.     

IL-2 and IL-6 secretion in dementia: correlation with type and severity of disease

The production of interleukin-2 (IL-2) and interleukin-6 (IL-6) by peripheral blood mononuclear cells (MNC) was assessed in patients with Alzheimer's disease (AD) who were subdivided into two groups — mild and moderately-severe — according to the severity of the disease, probable vascular dementia (VaD) patients and elderly control subjects. No differences in IL-2 secretion were found between mild AD patients and controls. However, there was a significant increase in IL-2 production both in the moderately-severe AD group and in the VaD group. IL-6 levels in AD patients of both groups were similar and significantly higher than those of VaD and controls. Our results suggest that increased levels of IL-2-production correlate with severity of the dementia, whereas increased levels of IL-6 production seem to be related to AD and thus may play a role in AD pathogenesis.     

Positive emotional style and subjective, cardiovascular and cortisol responses to acute laboratory stress

The relationships between positive emotional style and acute salivary cortisol and cardiovascular responses to laboratory stress tasks were examined in 40 young women (mean age=28.8 years). Positive emotional style (PES) was measured by aggregating daily positive mood rating scales over one week. Negative affect was assessed with the short form Profile of Mood States. Salivary cortisol was measured in response to two behavioural tasks, a 5 min speech task and a 5 min mirror tracing task. Blood pressure (BP) and heart rate responses were monitored using a Finometer during baseline, tasks and recovery. Higher PES was associated with more complete diastolic BP recovery (p=0.027) and lower acute cortisol response to stress (p=0.018), after adjusting for baseline measures, age, BMI and negative affect. Individuals with higher PES reported lower subjective tension during the tasks and perceived the tasks as more controllable. There were no differences in ratings of task involvement or in objective measures of task performance. A retrospective measure of positive affect (POMS vigour) was associated with diastolic BP recovery but not cortisol responses or subjective tension. The findings suggest that positive affective traits, assessed using repeated assessments of daily mood, are related to adaptive recovery from acute psychological stress. Our results reinforce evidence linking positive affect with adaptive diastolic BP recovery, while extending the results to cortisol. Investigations into the biological correlates of affective traits should consider utilising repeated measures of experienced affect.     

Association of plasma IL-6 and soluble IL-6 receptor levels with the Asp358Ala polymorphism of the IL-6 receptor gene in schizophrenic patients

Recent studies indicate a role of excessive interleukin-6 (IL-6) signaling in the pathogenesis of schizophrenia. A previous study reported a significant association of schizophrenia with the IL-6 receptor (IL-6R) gene Asp358Ala polymorphism, which is known to regulate circulating IL-6 and soluble IL-6R (sIL-6R) levels in healthy subjects. To further examine the influence of the polymorphism in schizophrenic patients, we compared the plasma levels of IL-6 and sIL-6R between schizophrenic patients and healthy controls for each genotype of the Asp358Ala polymorphism. Asp358Ala genotyping and plasma IL-6 level measurements were performed in 104 patients with schizophrenia and 112 healthy controls. Of these participants, 53 schizophrenic patients and 49 controls were selected for the measurement of plasma sIL-6R levels. A two-way factorial analysis of covariance was performed with the transformed plasma levels as the dependent variable, diagnosis and genotype as independent variables, and sex and age as covariates. No significant diagnosis × genotype interaction was observed for IL-6 and sIL-6R levels. The Ala allele of Asp358Ala was significantly associated with higher levels of both IL-6 and sIL-6R. IL-6 levels were significantly elevated in schizophrenic patients compared to those in controls, whereas no significant difference in sIL-6R levels was observed between schizophrenic patients and controls. Our findings suggest that the presence of schizophrenia is associated with elevated IL-6 levels, whereas sIL-6R levels are mainly predetermined by the Asp358Ala genotype and are not associated with the disease status. Increased IL-6 levels without alterations in sIL-6R levels may result in excessive IL-6 signaling in schizophrenia.     

Improved psychomotor performance in aged mice fed diet high in antioxidants is associated with reduced ex vivo brain interleukin-6 production

Psychomotor performance is decreased in the aged. This study investigated the relationship between brain oxidative stress, interleukin-6 (IL-6) production by brain tissue ex vivo and psychomotor deficits during aging, and the effects of feeding an antioxidant-rich diet on ex vivo brain IL-6 production and motor function in aged mice. Male BALBc mice reared in SPF conditions and ranging in age from 3 to 24 months were studied. There was a precipitous decline in motor function after 12 months of age and an increase in brain lipid peroxidation and IL-6 production by coronal brain slices ex vivo. In another study, 12-month-old mice were fed diets formulated to provide a disparate range of antioxidants. At 18 months of age psychomotor coordination, motor learning, and ex vivo brain IL-6 production were evaluated. Mice fed an antioxidant-rich diet had improved psychomotor coordination compared to mice fed diet adequate or low in antioxidants. When mice were tested on successive days, only those fed adequate and high antioxidants exhibited motor learning. Analysis of IL-6 production by coronal brain slices indicated that as dietary antioxidants increased, IL-6 production decreased. Collectively, these data indicate that antioxidants improve psychomotor performance in aged mice, and suggest antioxidants may be useful for reducing brain IL-6 production, which has been shown to increase in aged mice.     

脑梗死患者血清IL-6含量动态变化研究

目的 研究脑梗死患者血清ＩＬ－６含量变化及其意义。方法 我们用双抗体夹心ＥＬＩＳ地３０例糖梗死患者的表分别在发病１ｄ、３ｄ、７ｄ进行了连续检测,并用２０例健康人们作对照。结果 发现脑梗死患者血清ＩＬ－６含量在３个时间点均高于对照组（Ｐ〈０．０５）,在病程第１天血清ＩＬ－６含量高于第３天第７天（Ｐ〈０．０５）,且大面积脑梗死组血清ＩＬ－６含量高于小面积脑梗死组,神经功能受损重者血清ＩＬ－６含量高于神     

Asymmetrical modulation of interleukin-10 release in patients with intracerebral hemorrhage

The brain modulates the immune system in an asymmetrical way. Intracerebral hemorrhage triggers IL-6 and IL-10 release into blood. We measured (using ELISA method) serum IL-6 and IL-10 in acute phase of intracerebral hemorrhage in 11 patients with right hemisphere's hematoma and 15 patients with left hemisphere's hematoma. These patients did not differ significantly with respect to their age, size, and location of hematoma. IL-6 level was comparable in patients with left hematoma and patients with right hematoma, but patients with left hematoma had significantly higher level of IL-10 than patients with right hematoma. These results suggest that left and right hemisphere could modulate IL-10 release in different way.     

Serum levels of the pro-inflammatory interleukins 6 (IL-6) and -8 (IL-8) in patients with lumbar radicular pain due to disc herniation: A 12-month prospective study

Earlier studies indicate that lumbar radicular pain after disc herniation may be associated with a local inflammation induced by leakage of nucleus pulposus (NP) into the spinal canal and neuroforamen. In the present study we addressed the role of two interleukins, IL-6 and IL-8 in such long-lasting lumbar radicular pain. All 127 patients were recruited from Oslo University Hospital, Ullevål, Norway. At inclusion, 6 weeks and 12 months, serum concentrations of IL-6 and IL-8 were analyzed by enzyme-linked immunosorbent assay (ELISA) and pain intensity was reported on a 0–10 cm visual analog scale (VAS). Significantly higher levels of IL-6 and IL-8 in serum were found in patients with VAS ⩾3 at 12 months, than in patient with VAS <3 at 12 months (p ⩽ 0.01, test of between-subjects effect, repeated measures ANOVA, covariates for IL-6: age, smoking; covariates for IL-8: smoking, treatment). For the first time we show that chronic lumbar radicular pain may be associated with a persistent increase of the pro-inflammatory substances IL-6 and IL-8 in serum after disc herniation.     

Positive affect as a factor of resilience in the pain-negative affect relationship in patients with rheumatoid arthritis

OBJECTIVE: The purpose of this study is to examine positive affect (PA) as a factor of resilience in the relationships between pain and negative affect (NA) in a sample of patients with rheumatoid arthritis. METHODS: Forty-three patients (30 women; mean age, 57 years) were interviewed weekly by telephone for 8 weeks. Multilevel modeling was applied to study the within-week relationships among the variables. RESULTS: There was a Pain x PA interaction effect on NA (beta=-0.05, P<.01) indicating a weaker relationship between pain and NA in weeks with more PA. Pain (beta=0.37, P<.002), interpersonal stress (beta=2.42, P<.001), depression (beta=0.26, P<.01), average perceived stress (beta=10.80, P<.001), and also weekly PA (beta=-0.1, P<.01) had a main effect upon NA. CONCLUSION: Positive affect is most influential in reducing NA during weeks of higher pain and may be a factor of resilience, helping patients experiencing pain fluctuations as less distressful than at lower levels of PA.     

急性脑出血患者脑脊液TNF、IL-6、IL-8的变化及其临床意义

目的 观察脑出血患者脑脊液中肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)水平的动态变化,探讨其与脑出血的关系。方法 采用ELISA法分别测定32例脑出血患者病期<7d及病期>28d(5周内)的脑脊液TNF、IL-6、IL-8水平。结果 脑出血患者脑脊液TNF、IL-8水平较正常对照组增高,病期<7d者脑脊液TNF、IL-8水平较病期>28d升高显著(P<0.05);病期>28d TNF、IL-8有明显下降,但仍高于正常对照组(P<0.05);脑出血患者病期<7d及病期>28d脑脊液IL-6水平无明显差异(P>0.05),但均高于正常对照组。结论 脑脊液IL-8、INF、IL-6水平的动态变化与急性脑出血继发性脑损伤和修复过程密切相关。     

Self-rated health and interleukin-6: Longitudinal relationships in older adults

BackgroundBoth self-rated health (SRH) and inflammation are implicated in chronic diseases and premature mortality. Better SRH is associated with lower proinflammatory cytokines, but there is little evidence about whether this relationship is more stable or dynamic.ObjectiveTo study the between- and within-person associations between SRH and IL-6.MethodsOlder adults (N = 131; M_age = 75 years) rated their health and provided blood samples for analysis of IL-6 at separate occasions every 6 months over a period up to 5 years. Age, sex, BMI, neuroticism, and statin use were examined as covariates in multilevel models.ResultsIn bivariate models, better SRH, lower BMI, younger age, and female sex correlated with lower IL-6. In multilevel models, stable SRH (between-person differences; p < .001) but not dynamic SRH (within-person changes; p = .93) correlated with IL-6. The stable relationship persisted with demographic and health covariates in the model.ConclusionsBetter stable SRH but not dynamic SRH was robustly associated with lower IL-6 among older adults, lending support to previous cross-sectional findings on the relation between inflammatory markers and SRH. The findings suggest that trait-like mechanisms, rather than changes over a time scale of 6-month waves, govern this association. To further investigate the mechanisms behind the SRH–IL-6 association, studies with different measurement frequencies, higher within-person variability, and experimental approaches are warranted.     

Acute CSF interleukin-6 trajectories after TBI: Associations with neuroinflammation,polytrauma, and outcome

Traumatic brain injury (TBI) results in a significant inflammatory burden that perpetuates the production of inflammatory mediators and biomarkers. Interleukin-6 (IL-6) is a pro-inflammatory cytokine known to be elevated after trauma, and a major contributor to the inflammatory response following TBI. Previous studies have investigated associations between IL-6 and outcome following TBI, but to date, studies have been inconsistent in their conclusions. We hypothesized that cohort heterogeneity, temporal inflammatory profiles, and concurrent inflammatory marker associations are critical to characterize when targeting subpopulations for anti-inflammatory therapies. Toward this objective, we used serial cerebrospinal fluid (CSF) samples to generate temporal acute IL-6 trajectory (TRAJ) profiles in a prospective cohort of adults with severe TBI (n = 114). We examined the impact of injury type on IL-6 profiles, and how IL-6 profiles impact sub-acute (2 weeks–3 months) serum inflammatory marker load and long-term global outcome 6–12 months post-injury. There were two distinct acute CSF IL-6 profiles, a high and low TRAJ group. Individuals in the high TRAJ had increased odds of unfavorable Glasgow Outcome Scale (GOS) scores at 6 months (adjusted OR = 3.436, 95% CI: 1.259, 9.380). Individuals in the high TRAJ also had higher mean acute CSF inflammatory load compared to individuals in the low TRAJ (p ⩽ 0.05). The two groups did not differ with respect acute serum profiles; however, individuals in the high CSF IL-6 TRAJ also had higher mean sub-acute serum IL-1β and IL-6 levels compared with the low TRAJ group (p ⩽ 0.05). Lastly, injury type (isolated TBI vs. TBI + polytrauma) was associated with IL-6 TRAJ group (χ² = 5.31, p = 0.02). Specifically, there was 70% concordance between those with TBI + polytrauma and the low TRAJ; in contrast, isolated TBI was similarly distributed between TRAJ groups. These data provide evidence that sustained, elevated levels of CSF IL-6 are associated with an increased inflammatory load, and these increases are associated with increased odds for unfavorable global outcomes in the first year following TBI. Future studies should explore additional factors contributing to IL-6 elevations, and therapies to mitigate its detrimental effects on outcome.     

Psychometric Properties of the Positive and Negative Affect Scale for Children (PANAS-C) in Children with Anxiety Disorders

This study investigated the psychometric properties of the Positive and Negative Affect Scale for Children (PANAS-C) (Laurent et al. Psychol Asses 1: 326–338, 1999) in a sample of 139 children (ages 7–14 years) diagnosed with a principal anxiety disorder. Results from this study provided support for the convergent validity of the PANAS-C with established measures of childhood anxiety and depression. As predicted, negative affect was significantly associated with measures of anxiety and depression whereas positive affect was associated with depression. However, weaknesses in discriminant validity were found, most notably with regard to social anxiety. Consistent with previous research, social anxiety was significantly associated with low levels of positive affect (PA). Furthermore, results from regression analyses indicated that PA made a significant unique contribution to the prediction of social anxiety as well as depression scores. Findings are discussed with regard to the usefulness of the PANAS-C to differentiate anxiety and depression in children with anxiety disorders.     

糖皮质激素对重症肌无力患者血清肿瘤坏死因子及白介素-6水平的影响

目的 探讨糖皮质激素(GC)对重症肌无力(MG)患者血清肿瘤坏死因子(TNF)及白细胞介素-6(IL-6)水平的影响。方法 选择48 例MG 患者(治疗组),采用GC治疗,疗程1个月,观察治疗前后患者血清TNF及IL-6的水平,并在治疗前与42例健康者(对照组)比较。结果 治疗组治疗前患者血清TNF、IL-6水平均明显高于对照组(P<0.05),经GC治疗1个月后治疗组患者血清TNF、IL-6 水平降低,与治疗前比较有明显差异(P<0.05)。结论 GC可能通过抑制MG患者体内TNF及IL-6的产生来调节患者的免疫功能。     

白介素-6、10、12与精神分裂症临床特征的关系

目的 检测精神分裂症患者血浆IL-6、IL-10和IL-12水平,探讨其与精神分裂症临床特征的关系。方法 对57例精神分裂症患者和29例健康人,采用酶联免疫吸附法(ELSIA)检测其血浆IL-6、IL-10、IL-12水平,采用阳性和阴性症状评定量表(PANSS)评定患者的症状特征。结果 患者组血浆IL-12水平高于正常对照组(P<0.05),且与疾病的严重程度皇正相关;阴性症状组患者IL-6水平明显高于阳性症状组和正常对照组,而其IL-10水平则低于阳性症状组;急性或亚急性起病者血浆IL-10水平明显低于慢性起病组。 结论 精神分裂症存在细胞免疫异常,IL-12在精神分裂症的发病机制中起一定作用,IL-6和IL-10则与其部分临床特征有关。     

脑梗塞患者血浆白介素6,8的观察

为了研究脑梗塞后白介素６、８的变化及其意义，用双抗体夹心ＥＬＩＳＡ法对５５例脑梗塞患者血浆ＩＬ－６、８进行了检测。结果发现，急性期ＩＬ－８阳性率无增加，恢复期ＩＬ－８阳性率及含量明显增加。急性期和恢复期ＩＬ－６阳性率均有增加趋势，提示ＩＬ－６的变化较ＩＬ－８早，与脑缺血过程可能有关，而ＩＬ－８水平升高可能是机体隐匿性感染的结果     

Increased interleukin-6 mRNA expression in blood and cerebrospinal fluid mononuclear cells in multiple sclerosis

The increased intrathecal production of immunoglobulins within the cerebrospinal fluid (CSF) compartment commonly observed in multiple sclerosis (MS) implicates participation of B cell activating factors. One effect of the cytokine interleukin (IL) -6 is induction of immunoglobulin production by activated B cells. Employing in situ hybridization (ISH) with synthetic oligonucleotide probes, we measured numbers of IL-6 mRNA-expressing mononuclear cells (MNC) in blood and CSF from patients with MS, aseptic meningo-encephalitis (AM), and in blood from patients with other neurological diseases (OND) and healthy subjects. Numbers of IL-6 mRNA-expressing MNC were elevated in blood (mean frequency 1 per 33000 MNC) and even further enriched in the CSF (1 per 10000 MNC) of MS patients, and to a similar extent in AM patients' blood. Cultivation in the presence of myelin basic protein and proteolipid protein revealed strong augmentation of IL-6 mRNA-positive cells in MS but not in OND. The results suggest that IL-6 is one of several cytokines which are upregulated in MS, in particular locally in the CSF. A role of IL-6 in MS, whether disease-promoting or protective, remains unclear.