interleukin-8 and Delirium

Cerebrospinal fluid (CSF) analysis has great potential to advance understanding of delirium pathophysiology.. A systematic literature review of CSF studies of DSM or ICD delirium was performed.. In 8 studies of 235 patients, delirium was associated with: elevated serotonin metabolites, interleukin-8, cortisol, lactate and protein, and reduced somatostatin, β-endorphin and neuron-specific enolase. Elevated acetylcholinesterase predicted poor outcome after delirium and higher dopamine metabolites were associated with psychotic features.. No clear conclusions emerged, but the current literature suggests multiple areas for further investigation with more detailed studies.

Topics: Acetylcholinesterase; beta-Endorphin; Biomarkers; Brain; Delirium; Dopamine; Humans; Hydrocortisone; Interleukin-8; Lactic Acid; Phosphopyruvate Hydratase; Prognosis; Somatostatin

Delirium is an acute confusional state and a common postoperative morbidity. Prevalent in older adults, delirium occurs at other ages but it is unclear whether the pathophysiology and biomarkers for the condition are independent of age. We quantified expression of 273 plasma proteins involved in inflammation and cardiovascular or neurologic conditions in 34 middle-aged and 42 older patients before and one day after elective spine surgery. Delirium was identified by the 3D-CAM and comprehensive chart review. Protein expression was measure by Proximity Extension Assay and results were analyzed by logistic regression, gene set enrichment, and protein-protein interactions. Twenty-two patients developed delirium postoperatively (14 older; 8 middle-aged) and 89 proteins in pre- or 1-day postoperative plasma were associated with delirium. A few proteins (IL-8, LTBR, TNF-R2 postoperatively; IL-8, IL-6, LIF, ASGR1 by pre- to postoperative change) and 12 networks were common to delirium in both age groups. However, there were marked differences in the delirium proteome by age; older patients had many more delirium-associated proteins and pathways than middle-aged subjects even though both had the same clinical syndrome. Therefore, there are age-dependent similarities and differences in the plasma proteomic signature of postoperative delirium, which may signify age differences in pathogenesis of the syndrome.

Topics: Aged; Asialoglycoprotein Receptor; Delirium; Emergence Delirium; Humans; Interleukin-8; Middle Aged; Postoperative Complications; Proteomics

Neuroinflammation, where inflammatory cytokines are produced in excess, contributes to the pathogenesis of delirium. Microglial cells play a central role in neuroinflammation by producing and releasing inflammatory cytokines in response to infection, tissue damage and neurodegeneration. Dexmedetomidine (DEX) is a sedative, which reduces the incidence of delirium. Thus, we hypothesized that DEX may alleviate delirium by exhibiting anti-inflammatory action on microglia. In the present study, we investigated the anti-inflammatory action of DEX on human microglial HMC3 cells. The results indicated that DEX partially suppressed the IL-6 and IL-8 production by lipopolysaccharide (LPS)-stimulated HMC3 cells as well as the phosphorylation of p38 MAPK and IκB and the translocation of NF-κB. Furthermore, DEX substantially suppressed IL-6 and IL-8 production by unstimulated HMC3 cells as wells as the phosphorylation of p38 MAPK and IκB and the translocation of NF-κB. These observations suggest that DEX exhibits anti-inflammatory action on not only LPS-stimulated but also unstimulated microglial cells via the suppression of inflammatory signaling and cytokine production.

Topics: Anti-Inflammatory Agents; Cytokines; Delirium; Dexmedetomidine; Humans; I-kappa B Proteins; Interleukin-6; Interleukin-8; Lipopolysaccharides; Microglia; NF-kappa B; p38 Mitogen-Activated Protein Kinases

Esophagectomy is associated with postoperative delirium, but its pathophysiology is not well defined. We conducted this study to measure the relationship among serum biomarkers of inflammation and neuronal injury and delirium incidence and severity in a cohort of esophagectomy patients.. Blood samples were obtained from patients preoperatively and on postoperative days 1 and 3 and were analyzed for S100 calcium-binding protein B, C-reactive protein (CRP), interleukin (IL) 8 and IL-10, tumor necrosis factor-α, and insulin-like growth factor 1. Delirium was assessed twice daily using the Richmond Agitation Sedation Scale and Confusion Assessment Method for Intensive Care Unit. Delirium severity was assessed once daily with the Delirium Rating Scale-Revised-98.. Samples from 71 patients were included. Preoperative biomarker concentrations were not associated with postoperative delirium. Significant differences in change in concentrations from preoperatively to postoperative day 1 were seen in IL-8 (delirium, 38.6; interquartile range [IQR], 29.3-69.8; no delirium, 24.8; IQR, 16.0-41.7, P = .022), and IL-10 (delirium, 26.1; IQR, 13.9-36.7; no delirium, 12.4; IQR, 7.7-25.7; P = .025). Greater postoperative increase in S100 calcium-binding protein B (Spearman r = 0.289, P = .020) and lower levels of insulin-like growth factor 1 were correlated with greater delirium severity (Spearman r = -0.27, P = .040). Greater CRP change quartiles were associated with higher delirium incidence adjusting for severity of illness (odds ratio, 1.68; 95% confidence interval, 1.03-2.75; P = .037) or comorbidities (odds ratio, 1.70; 95% confidence interval, 1.05-2.76, P = .030).. Differences in change in serum CRP, IL-8, and IL-10 concentrations were associated with postoperative delirium, suggesting biomarker measurement early in the postoperative course is associated with delirium.

Topics: Biomarkers; C-Reactive Protein; Calcium-Binding Proteins; Delirium; Esophagectomy; Humans; Insulin-Like Growth Factor I; Interleukin-10; Interleukin-8

Postoperative delirium is associated with increases in the neuronal injury biomarker, neurofilament light (NfL). Here we tested whether two other biomarkers, glial fibrillary acidic protein (GFAP) and tau, are associated with postoperative delirium.. A total of 114 surgical patients were recruited into two prospective biomarker cohort studies with assessment of delirium severity and incidence. Plasma samples were sent for biomarker analysis including tau, NfL, and GFAP, and a panel of 10 cytokines. We determined a priori to adjust for interleukin-8 (IL-8), a marker of inflammation, when assessing associations between biomarkers and delirium incidence and severity.. GFAP concentrations showed no relationship to delirium. The change in tau from preoperative concentrations to postoperative Day 1 was greater in patients with postoperative delirium (P<0.001) and correlated with delirium severity (ρ=0.39, P<0.001). The change in tau correlated with increases in IL-8 (P<0.001) and IL-10 (P=0.0029). Linear regression showed that the relevant clinical predictors of tau changes were age (P=0.037), prior stroke/transient ischaemic attack (P=0.001), and surgical blood loss (P<0.001). After adjusting for age, sex, preoperative cognition, and change in IL-8, tau remained significantly associated with delirium severity (P=0.026). Using linear mixed effect models, only tau (not NfL or IL-8) predicted recovery from delirium (P<0.001).. The change in plasma tau was associated with delirium incidence and severity, and resolved over time in parallel with delirium features. The impact of this putative perioperative neuronal injury biomarker on long-term cognition merits further investigation.. NCT02926417 and NCT03124303.

Topics: Aged; Biomarkers; Delirium; Female; Glial Fibrillary Acidic Protein; Humans; Incidence; Interleukin-8; Male; Postoperative Complications; Predictive Value of Tests; Prospective Studies; Severity of Illness Index; tau Proteins; Time Factors

While delirium is associated with cognitive decline and dementia, there is limited evidence to support causality for this relationship. Clarification of how delirium may cause cognitive decline, perhaps through evidence of contemporaneous neuronal injury, would enhance plausibility for a causal relationship. Dose-dependence of neuronal injury with delirium severity would further enhance the biological plausibility for this relationship. We tested whether delirium is associated with neuronal injury in 114 surgical patients recruited to a prospective biomarker cohort study. Patients underwent perioperative testing for changes in neurofilament light, a neuronal injury biomarker, as well as a panel of 10 cytokines, with contemporaneous assessment of delirium severity and incidence. A subset of patients underwent preoperative MRI. Initially we confirmed prior reports that neurofilament light levels correlated with markers of neurodegeneration [hippocampal volume (ΔR2 = 0.129, P = 0.015)] and white matter changes including fractional anisotropy of white matter (ΔR2 = 0.417, P < 0.001) with similar effects on mean, axial and radial diffusivity) in our cohort and that surgery was associated with increasing neurofilament light from preoperative levels [mean difference (95% confidence interval, CI) = 0.240 (0.178, 0.301) log10 (pg/ml), P < 0.001], suggesting putative neuronal injury. Next, we tested the relationship with delirium. Neurofilament light rose more sharply in participants with delirium compared to non-sufferers [mean difference (95% CI) = 0.251 (0.136, 0.367) log10 (pg/ml), P < 0.001]. This relationship showed dose-dependence, such that neurofilament light rose proportionately to delirium severity (ΔR2 = 0.199, P < 0.001). Given that inflammation is considered an important driver of postoperative delirium, next we tested whether neurofilament light, as a potential marker of neurotoxicity, may contribute to the pathogenesis of delirium independent of inflammation. From a panel of 10 cytokines, the pro-inflammatory cytokine IL-8 exhibited a strong correlation with delirium severity (ΔR2 = 0.208, P < 0.001). Therefore, we tested whether the change in neurofilament light contributed to delirium severity independent of IL-8. Neurofilament light was independently associated with delirium severity after adjusting for the change in inflammation (ΔR2 = 0.040, P = 0.038). These data suggest delirium is associated with exaggerated increases in neurofilament light

Topics: Aged; Anisotropy; Brain; Cytokines; Delirium; Female; Hippocampus; Humans; Interleukin-8; Magnetic Resonance Imaging; Male; Neurofilament Proteins; Organ Size; Postoperative Complications; Preoperative Period; Prospective Studies; Severity of Illness Index; White Matter

Delirium is a common and serious complication in geriatric patients. The pathophysiology of delirium is not known.. The objective of the current study was to test the hypothesis that cerebrospinal fluid (CSF) levels of inflammatory markers at the time of spinal anesthesia for hip surgery are associated with delirium.. In total 133 hip fracture patients and 125 cognitively healthy controls undergoing elective surgery, together with 73 Alzheimer's disease (AD) dementia patients, were recruited at Oslo University Hospital and Diakonhjemmet Hospital, Oslo, Norway. Delirium was evaluated daily in hip fracture patients by the Confusion Assessment Method (CAM). Depression was evaluated by Cornell Scale for Depression in Dementia (CSDD). Tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), and interleukin-8 (IL-8) levels were measured in CSF using a Mesoscale Discovery (MSD) immunoassay.. Hip fracture patients had significantly higher IL-8 levels (p < 0.001) compared to cognitively healthy controls or patients with stable AD dementia. Furthermore, preoperative IL-8 levels were significantly higher (p = 0.013) in hip fracture patients who developed delirium (incident delirium) after surgery as compared to patients with no delirium. However, subgroup analyses showed that IL-8 levels were only significantly higher in delirium patients without dementia (p = 0.006). In contrast, depression subgroup analysis showed that IL-8 concentration was significantly higher (p = 0.002) in delirium patients with depression. Both TNF-α and IL-1β were undetected in most patients.. Our study suggests that IL-8 levels are associated with delirium onset and that underlying depression or dementia influences IL-8 levels.

Topics: Age Factors; Aged; Aged, 80 and over; Alzheimer Disease; Anesthesia; Biomarkers; Delirium; Dementia; Depression; Female; Healthy Volunteers; Hip Fractures; Humans; Inflammation; Interleukin-1beta; Interleukin-8; Male; Mental Status and Dementia Tests; Neuropsychological Tests; Psychiatric Status Rating Scales; Tumor Necrosis Factor-alpha

Topics: Aged; Aged, 80 and over; Biomarkers; Delirium; Female; Hip Fractures; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Middle Aged; Postoperative Complications; Postoperative Period; Reference Values; Tumor Necrosis Factor-alpha

The aim of this study was to investigate whether genetic polymorphisms in the interleukin-6 gene (IL6), the IL-6 receptor gene (IL6R), and the IL-8 gene (IL8) were associated with delirium in a population of acutely admitted older patients.. This was a prospective cohort study in the Academic Medical Center in Amsterdam, running from April, 2003, through August, 2008. A total of 881 patients, aged 65 years and older, acutely admitted to the medical department or to the surgical department following hip fracture, were included in the study. Delirium was diagnosed by the Confusion Assessment Method. Two single-nucleotide polymorphisms (SNPs) in the IL6 gene, one in the IL6R gene, and one in the IL8 gene were genotyped.. Fifty percent of the 115 surgical patients and 34% of the 605 medical patients experienced delirium. Delirious patients were older (82.8 years vs. 77.6 years) and had more frequent pre-existing functional (64% vs. 36%) or cognitive impairment (83% vs. 26%) (p < 0.001). The determination of polymorphisms had success rates between 87% and 96%. Rs1800697 and rs1800797 in the IL6 gene, rs8192284 in the IL6R gene, and rs4073 in the IL8 gene were not associated with the development of delirium.. Recent observations have indicated that IL-6 and IL-8 play a role in delirium in the elderly, but functional genetic variations in the IL6, IL6R, and IL8 genes were not associated with delirium. Still, the inflammatory hypothesis of delirium is gaining ground in the literature on the basis of recent animal research.

Topics: Aged; Aged, 80 and over; Delirium; Female; Genetic Variation; Humans; Interleukin-6; Interleukin-8; Male; Polymorphism, Genetic; Receptors, Interleukin-6

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

In independent studies delirium was associated with higher levels of cortisol, interleukin(IL)s, and S100B. The aim of this study was to simultaneously compare cortisol, IL-6, IL-8, and S100B levels in patients aged 65years and older admitted for hip fracture surgery with and without delirium. Cortisol, IL-6, IL-8, and S100B were assayed in repeated blood samples. 120 patients (mean age 84years, 62 patients with delirium) were included. Highest levels of IL-8 (27.1, 95% Confidence Interval (CI): 13.6-53.1pg/ml) and cortisol (666, 95% CI: 475-859nmol/L) were before delirium, but of IL-6 (84.3, 95% CI: 46.5-151.4pg/mL) and S100B (0.18, 95% CI: 0.12-0.24 microg/L) during delirium. In multivariable analysis cortisol, LogIL-6, and LogS100B were significantly associated with delirium, but adjusted for pre-existing cognitive impairment, only LogS100B remained significantly associated. Cortisol, IL-6 and S100B may have a role in the pathogenesis of delirium, but S100B is the strongest independent marker.

Topics: Aged; Aged, 80 and over; Biomarkers; Delirium; Female; Hip Fractures; Humans; Hydrocortisone; Immunoassay; Interleukin-6; Interleukin-8; Male; Nerve Growth Factors; S100 Calcium Binding Protein beta Subunit; S100 Proteins

To compare the time-course of cytokine levels in patients with and without delirium and investigate differences in cytokine concentrations in delirium subtypes.. Prospective cohort study.. Academic Medical Center, Amsterdam, 2005 through 2007.. Patients aged 65 and older admitted for surgery after hip fracture.. Experienced geriatric physicians used the Confusion Assessment Method to assess delirium and the Delirium Symptom Interview to assess delirium subtype. Tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta, IL-6, IL-8, IL-10, and IL-12 were assayed in repeated serum samples using a cytometric bead array immunoassay.. Of 221 admitted patients, 98 (mean age 84, 50 patients with delirium) were included, resulting in a total of 324 samples. Ninety-six percent of these samples had TNF-alpha, IL-1beta, and IL-10 levels below the reliable detection level. Differences between patients with and without delirium were observed in IL-6 (median 51 vs 36 pg/mL, P=.01) and IL-8 (median 15 vs 9 pg/mL, P=.03) levels. Changes over time in IL-6 and IL-8 levels in patients with delirium differed significantly from changes in levels in patients without delirium. The highest levels of IL-6 were present during delirium, and the highest levels of IL-8 were present before the development of delirium. Patients with the hyperactive (median 71 pg/mL) or mixed (median 73 pg/mL) subtype of delirium had higher IL-6 levels than patients with hypoactive delirium (median 16 pg/mL) (P=.02).. IL-6 and IL-8 may contribute to the pathogenesis of postoperative delirium in elderly people. IL-6 may play a role in the hyperactive behavior of delirium.

Topics: Aged; Aged, 80 and over; Arthroplasty, Replacement, Hip; Cohort Studies; Cytokines; Delirium; Female; Femoral Neck Fractures; Fracture Fixation, Internal; Hip Fractures; Humans; Interleukin-6; Interleukin-8; Male; Netherlands; Patient Admission; Postoperative Complications; Prospective Studies; Psychomotor Agitation; Statistics as Topic; Time Factors

This study aimed to examine the expression patterns of pro- and anti-inflammatory cytokines in elderly patients with and without delirium who were acutely admitted to the hospital.. All consecutive patients aged 65 years and older, who were acutely admitted to the Department of Internal Medicine of the Academic Medical Center, Amsterdam, a tertiary university teaching hospital, were invited. Members of the geriatric consultation team completed a multidisciplinary evaluation for all study participants within 48 h after admission, including cognitive and functional examination by validated measures of delirium, memory, and executive function. C-reactive protein and cytokines (IL-1beta, IL-6, TNF-alpha, IL-8, and IL-10) were determined within 3 days after admission.. In total, 185 patients were included; mean age was 79 years; 42% were male; and 34.6% developed delirium within 48 h after admission. Compared to patients without delirium, patients with delirium were older and had experienced preexistent cognitive impairment more often. In patients with delirium, significantly more IL-6 levels (53% vs. 31%) and IL-8 levels (45% vs. 22%) were above the detection limit as compared with patients who did not have delirium. After adjusting for infection, age, and cognitive impairment, these differences were still significant.. Proinflammatory cytokines may contribute to the pathogenesis of delirium in acutely admitted elderly patients.

Topics: Activities of Daily Living; Acute-Phase Reaction; Aged; Aged, 80 and over; Alzheimer Disease; Cytokines; Delirium; Disability Evaluation; Female; Geriatric Assessment; Humans; Interleukin-6; Interleukin-8; Male; Mental Status Schedule; Patient Admission; Patient Care Team; Reference Values

Acute confusional state (ACS) is an uncommon but severe central nervous system (CNS) syndrome in systemic lupus erythematosus (SLE) defined by clinical manifestations. To develop useful and reliable diagnostic tools for ACS, we evaluated the association of cerebral spinal fluid (CSF) tests with ACS and their predictive values for the diagnosis of ACS in SLE.. We performed a prospective study using a cohort of 59 patients with SLE and compared those with and without ACS. Associations between ACS and each CSF test [interleukin 6 (IL-6), IL-8, interferon-alpha, IgG index, and Q-albumin] were statistically evaluated. Each patient underwent all CSF evaluations.. ACS was diagnosed in 10 patients (ACS group), SLE-related CNS syndromes except ACS in 13, and no CNS syndromes in 36 (non-CNS group). CSF IL-6 levels in the ACS group were significantly higher than those in the non-CNS group (p < 0.05). A positive IgG index (p = 0.028) was significantly associated with ACS. No other test showed a significant association with ACS. The positive and negative predictive values for the diagnosis of ACS in SLE were 80% and 85% for elevated CSF IL-6 levels (> or = 31.8 pg/ml), and 75% and 83% for the IgG index, respectively.. No single CSF test had sufficient predictive value to diagnose ACS in SLE, although CSF IL-6 levels and the IgG index showed statistical associations with ACS. Use of CSF tests combined with careful history and clinical examinations is recommended for proper diagnosis of ACS in SLE.

Topics: Adolescent; Adult; Cohort Studies; Delirium; Female; Humans; Interferon-alpha; Interleukin-6; Interleukin-8; Lupus Erythematosus, Systemic; Male; Middle Aged; Predictive Value of Tests