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    Interleukin-1?, Interleukin-6, and Antagonist Interleukin-1receptor as Memory Impairment Risk Factor in Complex Partial Epilepsy

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    Memory impairment is one of the most common adverse following epilepsy, particularly complex partial epilepsy. Cytokines physiologically play an important role in memory impairment by preventing long term potentiation process in hypocampus. Several literatures have mentioned that IL-1b, IL-6 and antagonist receptor IL-1Ra are crucial cytokines in complex partial epilepsy. This study aims to find out whether high level of IL-1b and IL-6 as well as low level of IL-1Ra might be risk factors of memory impairment in complex partial epilepsy patient. This was a case control study, enrolling 30 complex partial epilepsy patients with memory impairment as case group and 30 complex partial epilepsy patients without memory impairment as control group. In this study, it was obtained that the mean of IL-1? level in case group was significantly higher compared to the control (2.74 ± 4.36 vs. 0.42 ± 0.18 pg/ml, p = 0.007). The mean of IL-6 in case group was significantly higher compare to control (5.89 ± 6.32 vs. 2.34 ± 1.80 pg/ml, p = 0.006). The mean of IL-1Ra level of the case group was not significantly higher compared to the control (519.81 ± 262.64 vs. 413.28 ± 106.85, p = 0.767). By applying bivariate analysis, McNemar's test, we observed that IL-1? with cut off point 0.63 pg/ml and OR = 70 is a risk factor of memory impairment in complex partial epilepsy indicated by p = 0.001. Similar result was also gained for IL-6 with cut off point 2.87 pg/ml and OR = 4.57 as a risk factor of memory impairment in complex partial epilepsy indicated by p = 0.007. Meanwhile, IL- 1Ra with cut off point 471 pg/ml and OR = 0.727 was not as a risk factor of memory impairment in complex partial epilepsy indicated by p = 0.573. It can be concluded that the high level of IL-1B and IL-6 were the risk factors of memory impairment in complex partial epilepsy patients. High level 1L-1B patient was 70 times higher risk of becoming memory impaired. High IL-6 patients will have the risk nearly 5 times higher. The low level of IL-1Ra does not as a risk factor in epilepsy patients for having the following memory impairment

    Paraneoplastic thrombocytosis in ovarian cancer

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    <p>Background: The mechanisms of paraneoplastic thrombocytosis in ovarian cancer and the role that platelets play in abetting cancer growth are unclear.</p> <p>Methods: We analyzed clinical data on 619 patients with epithelial ovarian cancer to test associations between platelet counts and disease outcome. Human samples and mouse models of epithelial ovarian cancer were used to explore the underlying mechanisms of paraneoplastic thrombocytosis. The effects of platelets on tumor growth and angiogenesis were ascertained.</p> <p>Results: Thrombocytosis was significantly associated with advanced disease and shortened survival. Plasma levels of thrombopoietin and interleukin-6 were significantly elevated in patients who had thrombocytosis as compared with those who did not. In mouse models, increased hepatic thrombopoietin synthesis in response to tumor-derived interleukin-6 was an underlying mechanism of paraneoplastic thrombocytosis. Tumorderived interleukin-6 and hepatic thrombopoietin were also linked to thrombocytosis in patients. Silencing thrombopoietin and interleukin-6 abrogated thrombocytosis in tumor-bearing mice. Anti–interleukin-6 antibody treatment significantly reduced platelet counts in tumor-bearing mice and in patients with epithelial ovarian cancer. In addition, neutralizing interleukin-6 significantly enhanced the therapeutic efficacy of paclitaxel in mouse models of epithelial ovarian cancer. The use of an antiplatelet antibody to halve platelet counts in tumor-bearing mice significantly reduced tumor growth and angiogenesis.</p> <p>Conclusions: These findings support the existence of a paracrine circuit wherein increased production of thrombopoietic cytokines in tumor and host tissue leads to paraneoplastic thrombocytosis, which fuels tumor growth. We speculate that countering paraneoplastic thrombocytosis either directly or indirectly by targeting these cytokines may have therapeutic potential. </p&gt

    Interleukin-6, age, and corpus callosum integrity.

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    The contribution of inflammation to deleterious aging outcomes is increasingly recognized; however, little is known about the complex relationship between interleukin-6 (IL-6) and brain structure, or how this association might change with increasing age. We examined the association between IL-6, white matter integrity, and cognition in 151 community dwelling older adults, and tested whether age moderated these associations. Blood levels of IL-6 and vascular risk (e.g., homocysteine), as well as health history information, were collected. Processing speed assessments were administered to assess cognitive functioning, and we employed tract-based spatial statistics to examine whole brain white matter and regions of interest. Given the association between inflammation, vascular risk, and corpus callosum (CC) integrity, fractional anisotropy (FA) of the genu, body, and splenium represented our primary dependent variables. Whole brain analysis revealed an inverse association between IL-6 and CC fractional anisotropy. Subsequent ROI linear regression and ridge regression analyses indicated that the magnitude of this effect increased with age; thus, older individuals with higher IL-6 levels displayed lower white matter integrity. Finally, higher IL-6 levels were related to worse processing speed; this association was moderated by age, and was not fully accounted for by CC volume. This study highlights that at older ages, the association between higher IL-6 levels and lower white matter integrity is more pronounced; furthermore, it underscores the important, albeit burgeoning role of inflammatory processes in cognitive aging trajectories

    Fetal and early neonatal interleukin-6 response

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    In 1998, a systemic fetal cytokine response, defined as a plasma interleukin-6 (IL-6) value above 11 pg/mL, was reported to be a major independent risk factor for the subsequent development of neonatal morbid events even after adjustments for gestational age and other confounders. Since then, the body of literature investigating the use of blood concentrations of IL-6 as a hallmark of the fetal inflammatory response syndrome (FIRS), a diagnostic marker of early-onset neonatal sepsis (EONS) and a risk predictor of white matter injury (WMI), has grown rapidly. In this article, we critically review: IL-6 biological functions; current evidence on the association between IL-6, preterm birth, FIRS and EONS; IL-6 reference intervals and dynamics in the early neonatal period; IL-6 response during the immediate postnatal period and perinatal confounders; accuracy and completeness of IL-6 diagnostic studies for EONS (according to the Standards for Reporting of Diagnostic Accuracy statement); and recent breakthroughs in the association between fetal blood IL-6, EONS, and WMI

    Differences in Inflammatory Markers between Nulliparous Women Admitted to Hospitals in Preactive vs Active Labor

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    Objective To determine whether labor-associated inflammatory markers differ between low-risk, nulliparous women in preactive vs active labor at hospital admission and over time. Study Design Prospective comparative study of low-risk, nulliparous women with spontaneous labor onset at term (n = 118) sampled from 2 large Midwestern hospitals. Circulating concentrations of inflammatory markers were measured at admission and again 2 and 4 hours later: namely, neutrophil, and monocyte counts; and serum inflammatory cytokines (interleukin -1β, interleukin-6, tumor necrosis factor-α, interleukin-10) and chemokines (interleukin-8). Biomarker concentrations and their patterns of change over time were compared between preactive (n = 63) and active (n = 55) labor admission groups using Mann-Whitney U tests. Results Concentrations of interleukin-6 and interleukin-10 in the active labor admission group were significantly higher than concentrations in the preactive labor admission group at all 3 time points. Neutrophil levels were significantly higher in the active group at 2 and 4 hours after admission. The rate of increase in neutrophils and interleukin-10 between admission and 2 hours later was faster in the active group (P \u3c .001 and P = .003, respectively). Conclusion Circulating concentrations of several inflammatory biomarkers are higher and their rate of change over time since admission is faster among low-risk, nulliparous women admitted to hospitals in active labor, as compared with those admitted in preactive labor. More research is needed to determine if progressive changes in inflammatory biomarkers might be a useful adjunct to improving the assessment of labor progression and determining the optimal timing of labor admission

    Influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training on the plasma cytokine response to maximum sustainable voluntary ventilation

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    The influence of oxidative stress, diaphragm fatigue, and inspiratory muscle training (IMT) on the cytokine response to maximum sustainable voluntary ventilation (MSVV) is unknown. Twelve healthy males were divided equally into an IMT or placebo (PLA) group, and before and after a 6-wk intervention they undertook, on separate days, 1h of (1) passive rest and (2) MSVV, whereby participants undertook volitional hyperpnea at rest that mimicked the breathing and respiratory muscle recruitment patterns commensurate with heavy cycling exercise. Plasma cytokines remained unchanged during passive rest. There was a main effect of time (P < 0.01) for plasma interleukin-1 (IL-1) and interleukin-6 (IL-6) concentrations and a strong trend (P = 0.067) for plasma interleukin-1 receptor antagonist concentration during MSVV. Plasma IL-6 concentration was reduced after IMT by 27 + 18% (main effect of intervention, P = 0.029), whereas there was no change after PLA (P = 0.753). There was no increase in a systemic marker of oxidative stress [DNA damage in peripheral blood mononuclear cells (PBMC)], and diaphragm fatigue was not related to the increases in plasma IL-1 and IL-6 concentrations. A dose-response relationship was observed between respiratory muscle work and minute ventilation and increases in plasma IL-6 concentration. In conclusion, increases in plasma IL-1 and IL-6 concentrations during MSVV were not due to diaphragm fatigue or DNA damage in PBMC. Increases in plasma IL-6 concentration during MSVV are attenuated following IMT, and the plasma IL-6 response is dependent upon the level of respiratory muscle work and minute ventilation

    Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension

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    BACKGROUND: Inflammation is a feature of pulmonary arterial hypertension (PAH), and increased circulating levels of cytokines are reported in patients with PAH. However, to date, no information exists on the significance of elevated cytokines or their potential as biomarkers. We sought to determine the levels of a range of cytokines in PAH and to examine their impact on survival and relationship to hemodynamic indexes. METHODS AND RESULTS: We measured levels of serum cytokines (tumor necrosis factor-alpha, interferon-gamma and interleukin-1beta, -2, -4, -5, -6, -8, -10, -12p70, and -13) using ELISAs in idiopathic and heritable PAH patients (n=60). Concurrent clinical data included hemodynamics, 6-minute walk distance, and survival time from sampling to death or transplantation. Healthy volunteers served as control subjects (n=21). PAH patients had significantly higher levels of interleukin-1beta, -2, -4, -6, -8, -10, and -12p70 and tumor necrosis factor-alpha compared with healthy control subjects. Kaplan-Meier analysis showed that levels of interleukin-6, 8, 10, and 12p70 predicted survival in patients. For example, 5-year survival with interleukin-6 levels of >9 pg/mL was 30% compared with 63% for patients with levels < or = 9 pg/mL (P=0.008). In this PAH cohort, cytokine levels were superior to traditional markers of prognosis such as 6-minute walk distance and hemodynamics. CONCLUSIONS: This study illustrates dysregulation of a broad range of inflammatory mediators in idiopathic and familial PAH and demonstrates that cytokine levels have a previously unrecognized impact on patient survival. They may prove to be useful biomarkers and provide insight into the contribution of inflammation in PAH

    PENGARUH OLAHRAGA PERNAFASAN TERHADAP PERUBAHAN KADAR BETA ENDORPHIN, INTERLEUKIN-2, INTERLEUKIN-4, INTERLEUKIN-6, IMUNOGLOBULIN G, dan HORMON KORTISOL (Sebuah Kajian Imunologi Pada Aktivitas Fisik)

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    The purpose of the research to expressing the changing of immunity at breathing exercise. This research represent of experimental. Device used “randomized pretest-posttest control group design. Population is student M A Mu'Alimin Yogyakarta. sample at every group 15 people. As unit analyse in this research taken away from blood cubiti vena. At this research which specified as variable depended as follows: rate of IL 6, IL 4, IL 2, cortisol, Beta Endorphin, and IgG. Training program conducted during 7 week, 3x /week, submaximal intensity, 6 set/session. This program executed on evening. Inspection laboratory of variable use ELISA method. The data analysis with descriptive statistic and inferensial with computerize SPSS for windows. Then statistical multivariat analysis and discriminant analysis. The result showed that sample characteristic data after normality test got p>0,05 normal, and homogeneous (p>0,05). Result of the moderator variable (tables 5.2) included in normal span. Dependent variable, after normality test got p>0,05, normal, and lavene’s test got p>0,05, homogeneous. Result of manova got p: 0,000, its meaning there are difference between group (Wilk Lambda, p<0,05). At discriminant matric structure can be explained the correlation between free variable and discriminant function formed that seen beta endorphin (0.501) its more strong relation with of discriminant function, followed by interleukin 6 (0.367). while other have less meaning. Discriminator variable representing function contribution every discriminator to modulation immunity emerging is beta endorphin, interleukin 6 and interleukin 4. Thereby hence beta endorphin have strongest contribution to increase immunity compared to the other variable. Conclusion: On the fact result, descriptive research which reported by Suparto, (2001), that breathing exercise can increase physical fitness and impenetrability of proven body manifestly. Breathing exercise increase beta endorphin, immunoglobulin G and Interleukin 6, while interleukin 2 and interleukin 4 do not happened increase. Cortisol nor happened degradation meaning, but at treatment and also control group there are indicate degradation of rate cortisol. Immunity Modulation which cause breathing exercise stressor got by 3 group owning strong contribution on the basis concept of psychoneuroimmunologic. Breathing exercise represent stimuli at path of limbic-hipothalamus-pituitary-adrenal (LHPA) generating immunomodulator process on the basis of physiobiologic paradigm which psychoneuroimmunologic concept. Keyword: breathing exercise, immunity, modulation FIK, 2007 (PEND. KEPELATIHAN

    Montmorency cherries reduce the oxidative stress and inflammatory responses to repeated days high-intensity stochastic cycling

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    This investigation examined the impact of Montmorency tart cherry concentrate (MC) on physiological indices of oxidative stress, inflammation and muscle damage across 3 days simulated road cycle racing. Trained cyclists (n = 16) were divided into equal groups and consumed 30 mL of MC or placebo (PLA), twice per day for seven consecutive days. A simulated, high-intensity, stochastic road cycling trial, lasting 109 min, was completed on days 5, 6 and 7. Oxidative stress and inflammation were measured from blood samples collected at baseline and immediately pre- and post-trial on days 5, 6 and 7. Analyses for lipid hydroperoxides (LOOH), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), interleukin-8 (IL-8), interleukin-1-beta (IL-1-β), high-sensitivity C-reactive protein (hsCRP) and creatine kinase (CK) were conducted. LOOH (p &lt; 0.01), IL-6 (p &lt; 0.05) and hsCRP (p &lt; 0.05) responses to trials were lower in the MC group versus PLA. No group or interaction effects were found for the other markers. The attenuated oxidative and inflammatory responses suggest MC may be efficacious in combating post-exercise oxidative and inflammatory cascades that can contribute to cellular disruption. Additionally, we demonstrate direct application for MC in repeated days cycling and conceivably other sporting scenario’s where back-to-back performances are required
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