interleukin-8 and Cerebrovascular-Disorders

Cerebrovascular disease (CeVD) and neurodegenerative dementia such as Alzheimer's disease (AD) are frequently associated comorbidities in the elderly, sharing common risk factors and pathophysiological mechanisms including neuroinflammation. Osteopontin (OPN) is an inflammatory marker found upregulated in vascular diseases as well as in AD. However, its involvement in vascular dementia (VaD) and pre-dementia stages, namely cognitive impairment no dementia (CIND), both of which fall under the spectrum of vascular cognitive impairment (VCI), has yet to be examined. Its correlations with inflammatory cytokines in cognitive impairment also await investigation. 80 subjects with no cognitive impairment (NCI), 160 with CIND and 144 with dementia were included in a cross-sectional study on a Singapore-based memory clinic cohort. All subjects underwent comprehensive clinical, neuropsychological and brain neuroimaging assessments, together with clinical diagnoses based on established criteria. Blood samples were collected and OPN as well as inflammatory cytokines interleukin (IL)-6, IL-8 and tumor necrosis factor (TNF) were measured using immunoassays. Multivariate regression analyses showed significant associations between increased OPN and VCI groups, namely CIND with CeVD, AD with CeVD and VaD. Interestingly, higher OPN was also significantly associated with AD even in the absence of CeVD. We further showed that increased OPN significantly associated with neuroimaging markers of CeVD and neurodegeneration, including cortical infarcts, lacunes, white matter hyperintensities and brain atrophy. OPN also correlated with elevated levels of IL-6, IL-8 and TNF. Our findings suggest that OPN may play a role in both VCI and neurodegenerative dementias. Further longitudinal analyses are needed to assess the prognostic utility of OPN in disease prediction and monitoring.

Topics: Aged; Alzheimer Disease; Atrophy; Biomarkers; Brain; Case-Control Studies; Cerebrovascular Disorders; Cognition; Cognitive Dysfunction; Cohort Studies; Cross-Sectional Studies; Dementia, Vascular; Female; Humans; Interleukin-6; Interleukin-8; Magnetic Resonance Imaging; Male; Middle Aged; Neuroimaging; Osteopontin; Singapore; Tumor Necrosis Factor-alpha; Vascular Diseases

BACKGROUND This study investigated the clinical effect of interventional therapy in ischemic cerebrovascular disease (ICD). MATERIAL AND METHODS A retrospective analysis was performed on 260 ICD patients who were divided into a control group (122 patients, conventional drug treatment) and an observation group (138 patients, interventional therapy plus conventional drug treatment). Enzyme-linked immunosorbent assay was used to examine the expression of IL-1β, IL-6, and NLR. Furthermore, neurological deficit scores and Barthel index scores as well as the correlation of IL-1β, IL-6 and NLR were examined in these 2 groups. RESULTS The expression of IL-1β, IL-6, and NLR significantly decreased in both groups after 1 week or 4 weeks of treatment compared with before treatment (P<0.05). Significant differences in neurological impairment scores were detected between these 2 groups after 4 weeks of treatment (P<0.05), and the control group showed higher neurological deficit scores than did the observation group (P<0.05). Barthel index scores were significantly higher after treatment than before treatment in the control and observation group (P<0.05), and the control group had lower Barthel index scores than did the observation group (P<0.05). Pearson correlation analysis showed that IL-1β, IL-6, and NLR expression were positively correlated in ICD patients (P<0.05). CONCLUSIONS Interventional surgery combined with conventional drug therapy can reduce serum IL-1β and IL-6 levels, decrease neurological impairment, and improve the quality of life of patients. The combined treatment group showed better outcomes than did the group that received the drug alone; therefore, combined therapy is suitable for promoting better clinical outcomes.

Topics: Adult; Aged; Brain Ischemia; Cerebrovascular Disorders; China; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Lymphocytes; Male; Middle Aged; Neutrophils; Quality of Life; Retrospective Studies; Treatment Outcome

Sodium butyrate (NaB) is a dietary microbial fermentation product of fiber and serves as an important neuromodulator in the central nervous system. In this study, we further investigated that NaB attenuated cerebral ischemia/reperfusion (I/R) injury in vivo and its possible mechanisms. NaB (5, 10 mg/kg) was administered intragastrically 3 h after the onset of reperfusion in bilateral common carotid artery occlusion (BCCAO) mice. After 24 h of reperfusion, neurological deficits scores were estimated. Morphological examination was performed by electron microscopy and hematoxylin-eosin (H&E) staining. The levels of oxidative stress and inflammatory cytokines were assessed. Apoptotic neurons were measured by TUNEL; apoptosis-related protein caspase-3, Bcl-2, Bax, the phosphorylation Akt (p-Akt), and BDNF were assayed by western blot and immunohistochemistry. The results showed that 10 mg/kg NaB treatment significantly ameliorated neurological deficit and histopathology changes in cerebral I/R injury. Moreover, 10 mg/kg NaB treatment markedly restored the levels of MDA, SOD, IL-1β, TNF-α, and IL-8. 10 mg/kg NaB treatment also remarkably inhibited the apoptosis, decreasing the levels of caspase-3 and Bax and increasing the levels of Bcl-2, p-Akt, and BDNF. This study suggested that NaB exerts neuroprotective effects on cerebral I/R injury by antioxidant, anti-inflammatory, and antiapoptotic properties and BDNF-PI3K/Akt pathway is involved in antiapoptotic effect.

Topics: Animals; Apoptosis; Brain Ischemia; Butyric Acid; Caspase 3; Cerebrovascular Disorders; Humans; Interleukin-8; Mice; Neuroprotective Agents; Oxidative Stress; Proto-Oncogene Proteins c-akt; Reperfusion Injury; Signal Transduction; Tumor Necrosis Factor-alpha

The most commonly occurring atherosclerotic manifestations are peripheral artery diseases (PAD). Immune-mediated processes contribute to the development of atherosclerosis, and affect the diseases outcome. The aim of the present study was to assess various immune-competent cells, cytokines and chemokines in patients with PAD and to evaluate whether the base immunological values reflect the subsequent development of cardio/cerebrovascular symptoms. One hundred sixty patients with PAD were followed-up for 42 months. At the time of enrolment, we determined blood lymphocyte subpopulations, both T-helper (Th)1/Th2-type intracytoplasmic cytokines and soluble cytokines, chemokines. Intracellular cytokines were measured on phorbol-myristate-acetate- and ionomycine- stimulated cells. Lymphocyte subgroups were quantified by flow cytometry, soluble cytokines by ELISA and intracellular cytokine levels were measured by flow cytometry. The ankle-brachial index (ABI), indicator of atherosclerosis, was also evaluated. The clinical results were correlated with the immune-parameters to assess the input of immune-inflammatory events in the propagation of vascular manifestation. CD4(+) T-cell proportions in patients with PAD with cerebro- cardio-vascular manifestations were decreased, which further reduced in patients with fatal outcome. Of circulating chemokines, IL-8 (CXCL-8) was increased in patients with subsequent cerebro- cardio-vascular manifestations, compared to those without the symptoms, and further raised in patients with fatal outcome. The percentage of interferon (IFN)-gamma positive cells showed clear negative correlation with ABI. We conclude that altered peripheral lymphocyte subsets and cytokine/chemokine imbalance play important roles in the proinflammatory cascade and reflect disease severity in patients with PAD.

Topics: Cardiovascular Diseases; Cerebrovascular Disorders; Cytokines; Female; Humans; Interleukin-8; Lymphocyte Activation; Male; Middle Aged; Peripheral Vascular Diseases; Risk Factors; T-Lymphocytes

We present a case report of encephalopathy associated with Salmonella urbana infection in a child. A 5-year-old boy was admitted to our clinic with convulsions and coma. Cerebrospinal fluid (CSF) interleukin-6 (IL-6) and IL-8 were elevated at onset and were decreased within normal limit on the fifth day. Residual neurological deficits included severe mental deficits and spastic tetraplegia. High levels of CSF proinflammatory cytokines might be related to central nervous system (CNS) disease activity. Although encephalopathy is a rare complication of non-typhi Salmonella infection, it should be borne in mind as an occasionally serious and potentially lethal disease.

Topics: Brain; Central Nervous System; Cerebrovascular Disorders; Child, Preschool; Humans; Inflammation; Interleukin-6; Interleukin-8; Male; Salmonella; Salmonella Infections; Time Factors; Tomography, X-Ray Computed

Topics: Adult; Aged; Aged, 80 and over; Bronchoalveolar Lavage Fluid; Cerebrovascular Disorders; Humans; Interleukin-8; Lymphocyte Count; Neutrophils

A growing body of evidence points out the potential role of inflammatory mechanisms in the pathophysiology of ischaemic brain damage. We have recently demonstrated that stroke patients display an intrathecal production of proinflammatory cytokines, such as IL-1beta and IL-6 already within the first 24 h after the beginning of symptoms (Tarkowski et al., 1995). The aim of the present study was to investigate patterns of local inflammatory responses as a consequence of acute stroke. Thirty stroke patients were studied prospectively on days 0-3, 7-9, 21-26 and after day 90 with clinical evaluations, radiological assessments and analysis of cerebrospinal fluid (CSF) cytokine levels. In addition, 15 healthy control CSF samples were used. Significantly increased CSF levels of IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-10 were observed early during the stroke with a peak on day 2 for the proinflammatory cytokines IL-8 and GM-CSF, and on day 3 for the immunoregulatory cytokine IL-10. Patients with a brain infarct predominantly located in the white matter showed significantly higher levels of IL-8 in CSF than patients with an infarct mainly located in the grey matter. Also, high levels of intrathecal tumour necrosis factor-alpha (TNF-alpha) were associated with the presence of white matter disease. Our study demonstrates an intrathecal production of proinflammatory and immunoregulatory cytokines in patients with stroke, supporting the notion of localized immune response to the acute brain lesion. A better understanding of the inflammatory response in stroke may lead to new treatment strategies.

Topics: Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Cytokines; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-10; Interleukin-8; Male; Middle Aged; Radiography; Tumor Necrosis Factor-alpha