interleukin-8 and Cognition-Disorders

Postoperative cognitive dysfunction (POCD) after cardiopulmonary bypass is a serious complication that can lead to personality changes, memory loss, reduction in the ability to learn, and other central nervous system dysfunctions. In recent years, there have been improvements in measures to protect the brain during surgery, although the incidence of cognitive dysfunction after cardiac surgery remains high (33 to 83% short-term and 20 to 60% long-term cognitive dysfunction). Despite the large amount of basic and clinical research on the incidence of POCD, its exact pathogenesis and complexity are not clear. Many studies have shown that the kynurenine pathway (KP) and cognitive function in humans are closely related. Some reports also show that the imbalance of some metabolites of the KP such as kynurenic acid and quinolinic acid (QUIN), which act in dynamic equilibrium under physiologic conditions, have effects on the central nervous system and can significantly affect cognitive function. Further studies have shown that inflammatory mediators may act on key enzymes of the KP causing KP-induced disorders. Severe inflammatory reaction occurs in patients undergoing cardiopulmonary bypass, which triggers metabolic pathways that are closely related to changes in cognitive function. In this review, we summarize that inflammation-induced metabolic kynurenine (KYN) pathway disorders are likely to have an important role in incidence of POCD after CPB surgery.

Topics: Biomarkers; Biosynthetic Pathways; Brain; Cardiopulmonary Bypass; China; Cognition Disorders; Humans; Incidence; Inflammation; Interleukin-1beta; Interleukin-6; Interleukin-8; Kynurenine; Postoperative Period; Tumor Necrosis Factor-alpha

Altered levels of cytokines and chemokines may play a role in cancer- and cancer treatment-related cognitive difficulties. In many neurodegenerative diseases, abnormal concentrations of cytokines and chemokines affect neuronal integrity leading to cognitive impairments, but the role of cytokines in chemotherapy-related cognitive difficulties in cancer patients is not well understood. Patients receiving doxorubicin-based (with cyclophosphamide, or cyclophosphamide plus fluorouracil; AC/CAF) chemotherapy or cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy report experiencing cognitive difficulties; because these regimens work by different modes of action, it is possible that they differentially affect cytokine levels.. This study examined the relationships between cytokine levels (i.e., IL-6, IL-8, and MCP-1) and type of chemotherapy among 54 early-stage breast cancer patients receiving AC/CAF or CMF. Cytokine levels were assessed at two time-points: prior to on-study chemotherapy cycle 2 (cycle 2) and after two consecutive chemotherapy cycles (prior to on-study cycle 4; cycle 4).. Analyses of variance using cycle 2 levels as a covariate (ANCOVA) were used to determine differences between chemotherapy groups. Levels of IL-6, IL-8, and MCP-1 increased in the AC/CAF group and decreased in the CMF group; the only significant between-group change was in IL-6 (p < 0.05).. These results, although preliminary based on the small sample size, suggest that AC/CAF chemotherapy is more cytokine inducing than CMF. Future studies should confirm these results and explore the distinct inflammatory responses elicited by different chemotherapy regimens when assessing cognitive function in cancer patients.

Topics: Adult; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemokine CCL2; Cognition Disorders; Double-Blind Method; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-6; Interleukin-8; Middle Aged; Time Factors

Chronic inflammation is a feature of Alzheimer´s disease (AD), resulting in excessive production of inflammatory mediators that can lead to neuroinflammation, contributing to alterations in Aβ production and deposition as Senile Plaques (SPs), and to neurofibrillary tangles (NFTs) formation, due to hyperphosphorylated Tau protein.. This work addressed the impact of the interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), two chemokines, on Tau phosphorylation; and also evaluated the chemokines' levels in plasma using samples from a regional cohort.. Human neuronal SH-SY5Y cells exposed to IL-8 and MCP-1 chemokines were monitored for their protein and phosphorylated protein levels by western blotting analysis. A serine/threonine protein phosphatase (PPs) activity assay was employed to monitor PPs activity. Subsequently, flow cytometry was used to monitor chemokines levels in plasma samples from individuals with cognitive deficits.. Chemokines' exposure resulted only in minor cytotoxicity effects on SH-SY5Y, and in increased Tau phosphorylation, particularly at the S396 residue. Tau phosphorylation correlated with PPs inhibition and was consistent with GSK3β phosphorylation-mediated inhibition. Subsequent analysis of plasma from individuals with cognitive deficits showed that IL-8 levels were decreased.. Data shows that both chemokines tested can exert an effect on GSK3β phosphorylation and modulate PPs activity, potentially resulting in increased Tau phosphorylation and subsequent NFTs formation. One can deduce that increased chemokines stimulation during chronic inflammation can exacerbate this event. The work contributes to a better understanding of the mode of action of these chemokines on AD pathogenesis and opens novel research avenues.

Topics: Alzheimer Disease; Chemokine CCL2; Cognition Disorders; Humans; Interleukin-8; Phosphoric Monoester Hydrolases; Phosphorylation; Plaque, Amyloid; tau Proteins

We aimed to study serum cytokine levels in 11 electrical status epilepticus in sleep (ESES) patients and 20 healthy control children. Patients showed significantly higher levels of interleukin (IL)-1α, IL-6, IL-10, chemokine (C-C motif) ligand (CCL)2 and chemokine (C-X-C motif) ligand (CXCL)8/IL-8 than controls, while macrophage migration inhibitory factor (MIF) and CCL3 were significantly lower. Follow-up analyses in five patients revealed a significant decrease of IL-6 levels after immunomodulating treatment. IL-6 changes were accompanied by clear improvement of electroencephalography (EEG) patterns and neuropsychological evaluation. We hypothesize that IL-6 correlates with disease activity and immunomodulating treatment efficacy.

Topics: Adolescent; Case-Control Studies; Chemokine CCL2; Chemokine CCL3; Child; Child, Preschool; Cognition Disorders; Cytokines; Electroencephalography; Female; Glucocorticoids; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Inflammation; Interleukin-10; Interleukin-1alpha; Interleukin-6; Interleukin-8; Intramolecular Oxidoreductases; Language Disorders; Macrophage Migration-Inhibitory Factors; Male; Methylprednisolone; Neuropsychological Tests; Prednisolone; Sleep Wake Disorders; Status Epilepticus; Syndrome; Treatment Outcome

Microbial translocation from the gut is associated with immune dysfunction, persistent inflammation, and likely plays a role in the pathogenesis of neurocognitive dysfunction during HIV infection. (1→3)-β-D-Glucan (BDG) is a component of most fungal cell walls and might be a useful indicator of gut mucosal barrier impairment. The objective of this study was to evaluate whether higher blood BDG levels correlate with impaired neurocognitive functioning in a cohort of HIV-infected adults with suppressed levels of HIV RNA in blood plasma. In this cross-sectional cohort study, we measured levels of BDG in blood plasma and cerebrospinal fluid (CSF) supernatant samples in a cohort of adults with acute/early HIV infection, who initiated antiretroviral therapy (ART) during the earliest phase of infection and achieved suppressed levels of HIV RNA in blood plasma (<50 copies/mL) thereafter. We compared BDG with established biomarkers of microbial translocation, immune activation, and cognitive dysfunction (evaluated by global deficit score). We found that higher blood BDG levels were significantly related to higher global deficit scores, reflecting worse neurocognitive performance (Spearman r = 0.47; P = 0.042) among HIV-infected adults with suppressed viral loads who initiated ART early in infection. Two CSF samples presented elevated BDG levels. Interestingly, these 2 samples originated from the 2 subjects with the highest global deficit scores of the cohort. BDG may be a promising independent biomarker associated with neurocognitive functioning in virologically suppressed HIV-infected individuals.

Topics: Adult; Aged; Anti-HIV Agents; Bacterial Translocation; beta-Glucans; Biomarkers; CD4 Lymphocyte Count; Cognition Disorders; Cross-Sectional Studies; Female; HIV; HIV Infections; Humans; Interleukin-8; Lipopolysaccharide Receptors; Male; Middle Aged; Neuropsychological Tests; Retrospective Studies; RNA, Viral; Severity of Illness Index

Population-based studies have demonstrated the association of inflammation and cognitive impairment. However, few studies to date have examined this association in ischemic stroke patients.. The study aims to determine the association between inflammatory markers and cognitive impairment.. Ischemic stroke patients with baseline neuropsychological assessments at three-months poststroke were followed up with annual neuropsychological assessments for up to five-years. Inflammatory markers (C-reactive protein, interleukin 1β, interleukin 6, interleukin 8, interleukin 10, interleukin 12, and tumor necrosis factor-α) were assayed, and logistic regression analyses were performed to determine associations between inflammatory markers and both baseline cognitive status and subsequent cognitive decline.. There were 243 ischemic stroke patients in the study. In multivariable ordinal logistic regression analysis, age, education, ethnicity, stroke subtype, and interleukin 8 (OR 1.23 CI 1.05-1.44) levels were independently associated with baseline cognitive status. In multivariable logistic regression analyses, age, gender, recurrent strokes, and interleukin 12 (OR 25.02 CI 3.73 to 168.03) were independent predictors of subsequent cognitive decline.. Following ischemic stroke, higher serum interleukin 8 is independently associated with baseline cognitive impairment while higher serum interleukin 12 is associated with subsequent cognitive decline.

Topics: Aged; Blood Chemical Analysis; Brain Ischemia; Cognition Disorders; Female; Follow-Up Studies; Humans; Interleukin-12; Interleukin-8; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neuropsychological Tests; Stroke

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive loss of cognitive abilities. Epigenetic modification, oxidative stress, and inflammation play an important role in the pathogenesis of the disease. We aimed to detect noninvasive peripheral biomarkers with a high degree of sensitivity and specificity in diagnosis and progression of AD.. A total of 25 elderly patients with AD and 25 healthy control participants were selected and subjected to cognitive assessment and laboratory measures including histone deacetylases (HDACs), copper, and interleukin 8 (IL-8) levels.. The levels of HDACs, copper, and IL-8 were significantly higher in patients with AD (P < .001) and had a significant negative effect on all cognitive assessment tests. Receiver-operating curve (ROC) analysis revealed that HDACs and copper levels had higher sensitivity and specificity.. Plasma levels of HDACs and copper may be used as peripheral biomarkers in diagnosis of AD, while IL-8 level could be a useful biomarker in following AD progression.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Biomarkers; Cognition Disorders; Copper; Disease Progression; Down-Regulation; Female; Geriatric Assessment; Histone Deacetylases; Humans; Interleukin-8; Male; Neuropsychological Tests; Psychiatric Status Rating Scales; Severity of Illness Index; Up-Regulation

In the current era of highly active antiretroviral therapy (HAART), the incidence of HIV dementia has declined, but the prevalence of HIV-associated neurocognitive disorder (HAND) remains high. HIV-induced systemic and localized inflammation is considered to be one of the mechanisms of HAND. Changes in cytokine levels in the cerebrospinal fluid (CSF) during HIV infection might help to identify HAND. To investigate whether the cytokine profile of the CSF during HIV infection could be used as a biomarker of HAND, we compared cytokine levels in the CSF of HIV-infected cases with and without neurocognitive impairment. Cytokine concentrations in the CSF were measured by quantification bioassays (Luminex xMAP). HIV-infected cases with neurocognitive impairment demonstrated higher levels of interleukin (IL)-8, monocyte chemotactic protein (MCP)-1, induced protein (IP)-10, and granulocyte colony-stimulating factor (G-CSF) in the CSF than those without neurocognitive impairment (G-CSF (p = 0.0003), IL-8 (p = 0.0046), IP-10 (p < 0.0001), and MCP-1 (p < 0.0001)). There was no significant impact of HAART on cytokine levels in the CSF, except for IP-10, which was higher in HAART-treated patients with impaired cognition (p = 0.0182). Findings from this preliminary study suggest that elevated levels of the cytokines IL-8, MCP-1, G-CSF, and IP-10 in the CSF are associated with neurocognitive impairment in HIV infection, and these cytokines likely represent a biomarker profile for HAND.

Topics: Adult; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Biomarkers; Chemokine CCL2; Chemokine CXCL10; China; Cognition Disorders; Female; Granulocyte Colony-Stimulating Factor; HIV Infections; Humans; Interleukin-8; Male; Middle Aged; Severity of Illness Index

Neurodegenerative processes associated with Alzheimer's disease (AD) are accompanied by reactive astrogliosis and microglia activation and a role for chronic inflammation in the brain degeneration of these patients has been suggested. Moreover impaired immune functions in AD brains might also influence the disease's progression. Therefore, it is of interest to further characterized inflammatory molecules in the peripheral blood of patients with AD and its relationship with cognitive decline. A complex picture emerged in this pilot study and IL-8, IFN-gamma, MCP-1 and VEGF levels were increased in AD. Levels of P-selectin and L-selectin were decreased in AD and lowest in AD patients with highest cognitive decline. Our findings suggest that these molecules may induce alterations of endothelial regulation and influence neurodegenerative processes of AD.

Topics: Alzheimer Disease; Brain; Chemokine CCL2; Cognition Disorders; Female; Humans; Interferon-gamma; Interleukin-8; L-Selectin; Male; P-Selectin; Pilot Projects; Vascular Endothelial Growth Factor A

Delirium occurs frequently in critically ill patients and is associated with disease severity and infection. Although several pathways for delirium have been described, biomarkers associated with delirium in intensive care unit (ICU) patients is not well studied. We examined plasma biomarkers in delirious and nondelirious patients and the role of these biomarkers on long-term cognitive function.. In an exploratory observational study, we included 100 ICU patients with or without delirium and with ("inflamed") and without ("noninflamed") infection/systemic inflammatory response syndrome (SIRS). Delirium was diagnosed by using the confusion-assessment method-ICU (CAM-ICU). Within 24 hours after the onset of delirium, blood was obtained for biomarker analysis. No differences in patient characteristics were found between delirious and nondelirious patients. To determine associations between biomarkers and delirium, univariate and multivariate logistic regression analyses were performed. Eighteen months after ICU discharge, a cognitive-failure questionnaire was distributed to the ICU survivors.. In total, 50 delirious and 50 nondelirious patients were included. We found that IL-8, MCP-1, procalcitonin (PCT), cortisol, and S100-β were significantly associated with delirium in inflamed patients (n = 46). In the noninflamed group of patients (n = 54), IL-8, IL-1ra, IL-10 ratio Aβ1-42/40, and ratio AβN-42/40 were significantly associated with delirium. In multivariate regression analysis, IL-8 was independently associated (odds ratio, 9.0; 95% confidence interval (CI), 1.8 to 44.0) with delirium in inflamed patients and IL-10 (OR 2.6; 95% CI 1.1 to 5.9), and Aβ1-42/40 (OR, 0.03; 95% CI, 0.002 to 0.50) with delirium in noninflamed patients. Furthermore, levels of several amyloid-β forms, but not human Tau or S100-β, were significantly correlated with self-reported cognitive impairment 18 months after ICU discharge, whereas inflammatory markers were not correlated to impaired long-term cognitive function.. In inflamed patients, the proinflammatory cytokine IL-8 was associated with delirium, whereas in noninflamed patients, antiinflammatory cytokine IL-10 and Aβ1-42/40 were associated with delirium. This suggests that the underlying mechanism governing the development of delirium in inflamed patients differs from that in noninflamed patients. Finally, elevated levels of amyloid-β correlated with long-term subjective cognitive-impairment delirium may represent the first sign of a (subclinical) dementia process. Future studies must confirm these results.The study was registered in the Clinical Trial Register (NCT00604773).

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Chemokine CCL2; Chi-Square Distribution; Cognition Disorders; Critical Illness; Delirium; Female; Humans; Hydrocortisone; Inflammation; Interleukin-8; Interleukins; Logistic Models; Male; Middle Aged; Nerve Growth Factors; Protein Precursors; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Statistics, Nonparametric

Recent studies indicate that chronic inflammation plays a pathogenic role in both the central nervous system (CNS) and periphery in Alzheimer's disease (AD). We have screened for cytokines differentially produced by peripheral blood mononuclear cells (PBMCs) isolated from subjects with mild cognitive impairment (MCI) and mild AD subjects who had progressed from MCI using a commercially available cytokine array. Following determination of expressed cytokines, we quantified levels of the proinflammatory cytokines TNF-alpha, IL-6, and IL-8, and the anti-inflammatory cytokine IL-10 using flow cytometry. We have found a significant increase in the levels of IL-6, IL-8, and IL-10 produced by PBMCs stimulated for 24 h with phytohemagglutinin (PHA) in MCI subjects compared to healthy elderly controls. However, in PBMCs stimulated for 48 h with lipopolysaccharide (LPS), lower TNF-alpha/IL-10, IL-6/IL-10, and IL-8/IL-10 ratios were seen in MCI subjects. There were no differences in plasma levels of IL-8 between aged controls, MCI, and mild AD, and the levels of circulating IL-6 and IL-10 were below detection limits. Our data indicate that changes in cytokine production by PBMCs may be detected early in MCI, and an alteration of the immune response may precede clinical AD.

Topics: Aged; Alzheimer Disease; Cells, Cultured; Cognition Disorders; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Interleukins; Leukocytes, Mononuclear; Male; Receptors, Cytokine; Tumor Necrosis Factor-alpha

Topics: Age of Onset; Aged; Alzheimer Disease; Biomarkers; Cell Death; Cerebrospinal Fluid; Chemokine CCL2; Chemokines; Cognition Disorders; Dementia; Disease Progression; Female; Humans; Interleukin-8; Male; Middle Aged; Nerve Degeneration; Neurons; Predictive Value of Tests; Sex Factors; Spinal Puncture; Up-Regulation

Immunoreactivity for several chemokines and for their related receptors has been demonstrated in resident cells of the central nervous system, and the up-regulation of some of them is associated with pathological changes found in Alzheimer disease (AD).. To determine interferon-gamma-inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP-1), and interleukin 8 (IL-8) levels in cerebrospinal fluid (CSF) from subjects with amnestic mild cognitive impairment (MCI) and patients with AD as compared with age-matched controls.. Thirty-eight subjects with amnestic MCI, 36 patients with AD, and 41 age-matched subjects with noninflammatory affections of the nervous system.. Evaluation of CSF chemokine production at time of diagnosis of MCI and AD; correlation with clinical and personal data. Longitudinal evaluation of subjects with MCI until conversion to AD.. Cerebrospinal fluid IP-10 concentration was significantly increased in patients with MCI and mild AD but not in patients with severe AD (Mini-Mental State Examination score <15), whereas MCP-1 and IL-8 levels were increased in patients with MCI and all patients with AD. A significant positive correlation between Mini-Mental State Examination score and CSF IP-10 or MCP-1 concentration was observed in patients with AD. No correlation between IP-10 levels and age was found, whereas MCP-1 and IL-8 levels correlated positively with age. Out of 38 subjects with MCI, 19 developed AD within a 1- to 3-year follow-up.. The presence of inflammatory molecules is likely to be a very early event in AD pathogenesis, even preceding the clinical onset of the disease, as demonstrated by subjects with MCI who developed AD over time. Interferon-gamma-inducible protein 10 is specifically increased in MCI and seems to decrease with the progression of AD, whereas MCP-1 and IL-8 are up-regulated also in late stages of the disease, suggesting a role in phases in which neurodegeneration is prevalent.

Topics: Aged; Alzheimer Disease; Brain; Cerebrospinal Fluid Proteins; Chemokine CCL2; Chemokine CXCL10; Chemokines; Chemokines, CXC; Cognition Disorders; Encephalitis; Female; Humans; Interleukin-8; Male; Middle Aged; Neuropsychological Tests; Predictive Value of Tests; Statistics as Topic; Up-Regulation