interleukin-8 and Multiple-Sclerosis--Relapsing-Remitting

Glucocorticosteroids (GS) are standard treatment of multiple sclerosis (MS) relapse, but no superiority of any commonly used doses is known. The aim of present study was to evaluate mRNA expression for two cytokines: IL-6 and IL-8. Ethylenediaminetetraacetic acid blood samples from 35 MS relapse patients were obtained before therapy, after 7, 14 days, and 3 months from treatment start (500 versus 1000 mg for 5 days). Significant neurological improvement measured with EDSS was independent to GS dose. Changes of mRNA cytokines expression were more evident in higher dose group but for IL-6 mainly in females.

Topics: Adult; Female; Glucocorticoids; Humans; Injections, Intravenous; Interleukin-6; Interleukin-8; Male; Methylprednisolone; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Neuroprotective Agents; Recurrence; RNA, Messenger; Sex Factors

Chemokines are involved in the pathogenesis of multiple sclerosis. The aim of the study was to evaluate the effects of immunosuppressive therapy on production of two proinflammatory chemokines--interleukin-8 (IL-8) and RANTES (regulated on activation, normal T cell expressed and secreted).. Twenty-five patients with relapsing-remitting multiple sclerosis were treated with 2-chlorodeoxyadenosine (Cladribine), administered subcutaneously in 6 cycles repeated every 5 weeks. IL-8 and RANTES levels were measured by the enzyme-linked immunoassay (ELISA) method in serum and cerebrospinal fluid (CSF) before and after treatment.. After Cladribine treatment the levels of IL-8 decreased significantly in CSF only, whereas the RANTES levels decreased significantly both in CSF and serum.. Our results suggest that Cladribine therapy might modify the circulating level of RANTES.

Topics: Adult; Chemokine CCL5; Cladribine; Female; Humans; Immunosuppressive Agents; Injections, Subcutaneous; Interleukin-8; Male; Multiple Sclerosis, Relapsing-Remitting

Individual genetic variability may influence the course of multiple sclerosis (MS). The interleukin (IL)-8C>T rs2227306 single nucleotide polymorphism (SNP) regulates IL-8 activity in other clinical conditions; however, its role in MS has never been investigated.. To explore the association between IL-8 SNP rs2227306, cerebrospinal fluid (CSF) IL-8 concentrations, clinical, and radiological characteristics in a group of newly diagnosed MS patients.. In 141 relapsing-remitting (RR)-MS patients, rs2227306 polymorphism, CSF levels of IL-8, clinical, and demographical characteristics were determined. In 50 patients, structural magnetic resonance imaging (MRI) measures were also assessed.. We describe for the first time a role of SNP rs2227306 of IL-8 gene in regulating the expression and the activity of this inflammatory cytokine in MS.

Topics: Cytokines; Humans; Interleukin-8; Magnetic Resonance Imaging; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting

Clinical deterioration of relapsing-remitting MS (RR-MS) patients reflects not only the number and severity of overt inflammatory and demyelinating episodes, but also subtle central damage caused by persistent exposure to inflammatory molecules.. To explore the correlation between levels of CSF inflammatory molecules at the time of diagnosis and both demographic and clinical characteristics of a large sample of RR-MS patients, as well as the predictive value of cytokine levels on their prospective disease course.. In 205 patients diagnosed with RR-MS, we measured at the time of diagnosis the CSF levels of inflammatory molecules. Clinical and MRI evaluation was collected at the time of CSF withdrawal and during a median follow-up of 3 years.. The time interval between the first anamnestic episode of focal neurological dysfunction and RR-MS diagnosis was the main factor associated with high CSF levels of IL-6 and IL-8. Furthermore, elevated CSF levels of these cytokines correlated with enhanced risk of clinical and radiological disease reactivation, switch to second-line treatments, and with disability progression in the follow-up.. Delayed diagnosis and treatment initiation are associated with higher CSF levels of IL-6 and IL-8 in RR-MS, leading to worsening disease course and poor response to treatments.

Topics: Adult; Biomarkers; Disease Progression; Female; Follow-Up Studies; Humans; Interleukin-6; Interleukin-8; Magnetic Resonance Imaging; Male; Multiple Sclerosis, Relapsing-Remitting; Prognosis; Prospective Studies; Time-to-Treatment

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder of the central nervous system (CNS). Reliable biomarkers are urgently needed for its diagnosis and management, and as clues to its pathogenesis, in which EBV is implicated.. To measure IgG antibodies against EBV nuclear antigen-1 (EBNA-1) and innate inflammation status in paired serum and cerebrospinal fluid (CSF) samples from untreated relapsing-remitting MS (RRMS) patients.. Anti-EBNA-1 IgG titers and IL-8, IL-1β, IL-6, IL-10, TNF-α and IL-12p70 cytokine levels were measured in 20 untreated RRMS-patients and 17 healthy controls.. We found higher serum anti-EBNA-1 IgG and IL-8 levels in RRMS-patients than in healthy controls. Interestingly, levels of IL-8 - relative to total protein - were much higher in the CSF, whereas the anti-EBNA-1 antibodies were significantly higher in the sera. More detailed analysis showed that anti-EBNA-1 antibodies relative to total IgG were also higher in the serum in the majority of RRMS patients compared to CSF. Levels of anti-EBNA-1 IgG and IL-8 showed a strong correlation between serum and CSF.. These findings in newly diagnosed RRMS-patients imply anti-EBNA-1 antibody production mainly in the periphery and innate immune responses preferentially in the CNS. Both their potential as disease biomarkers and their implications for the pathogenesis of MS warrant further investigation.

Topics: Adolescent; Adult; Animals; Cytokines; Epstein-Barr Virus Nuclear Antigens; Female; Humans; Immunoglobulin G; Interleukin-8; Male; Mice; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Statistics as Topic; Young Adult

Subtle diffuse intrathecal inflammation is undetectable by conventional neuroimaging, and could influence multiple sclerosis (MS) disease course.. To explore the role of subclinical persisting intrathecal inflammation in radiologically isolated syndrome (RIS) or clinically isolated syndrome (CIS) conversion to MS, and in early MS disease reactivation.. One-hundred ninety-three subjects with RIS, CIS, relapsing-remitting (RR), or primary progressive (PP) MS were included, along with 76 matched controls. Cerebrospinal fluid (CSF) levels of interleukin-8 (IL-8), a major proinflammatory cytokine, were measured as a biomarker of intrathecal inflammation. Patients were followed up for 2 years. Clinical and imaging measures of disease progression were recorded.. High central contents of IL-8 were associated to clinical progression in subjects with RIS, and to the risk of conversion to MS in subjects with CIS. Asymptomatic intrathecal inflammation placed subjects at risk for MS conversion, even regardless lesion load. CSF IL-8 levels were higher in RR MS with high disease activity. Higher number of relapses in the first two years since diagnosis and shorter first inter-attack intervals were observed in patients with high levels of IL-8.. IL-8 might provide utility in determining the presence of active intrathecal inflammation, and could be important in diagnostically undefined cases.

Topics: Adult; Biomarkers; Demyelinating Diseases; Disease Progression; Female; Follow-Up Studies; Humans; Inflammation; Interleukin-8; Male; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting

The management of complex patients with neuroimmunological diseases is hindered by an inability to reliably measure intrathecal inflammation. Currently implemented laboratory tests developed >40 years ago either are not dynamic or fail to capture low levels of central nervous system (CNS) inflammation. Therefore, we aimed to identify and validate biomarkers of CNS inflammation in 2 blinded, prospectively acquired cohorts of untreated patients with neuroimmunological diseases and embedded controls, with the ultimate goal of developing clinically useful tools.. Because biomarkers with maximum utility reflect immune phenotypes, we included an assessment of cell specificity in purified primary immune cells. Biomarkers were quantified by optimized electrochemiluminescent immunoassays.. Among markers with cell-specific secretion, soluble CD27 is a validated biomarker of intrathecal T-cell activation, with an area under the receiver operating characteristic curve of 0.97. Comparing the quantities of cerebrospinal fluid (CSF) immune cells and their respective cell-specific soluble biomarkers (released by CSF cells as well as their counterparts in CNS tissue) provided invaluable information about stationary CNS immune responses, previously attainable via brain biopsy only. Unexpectedly, progressive and relapsing-remitting multiple sclerosis (MS) patients have comparable numbers of activated intrathecal T and B cells, which are preferentially embedded in CNS tissue in the former group.. The cell-specific biomarkers of intrathecal inflammation may improve diagnosis and management of neuroimmunological diseases and provide pharmacodynamic markers for future therapeutic developments in patients with intrathecal inflammation that is not captured by imaging, such as in progressive MS.

Topics: Adult; Aged; B-Lymphocytes; Biomarkers; Case-Control Studies; Cerebrospinal Fluid; Cohort Studies; Female; Humans; Inflammation; Interleukin-12 Subunit p40; Interleukin-8; Lipopolysaccharide Receptors; Lymphocyte Count; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Nervous System Diseases; Prospective Studies; Receptors, Complement 3d; T-Lymphocytes; Tumor Necrosis Factor Receptor Superfamily, Member 7; Young Adult

Acute optic neuritis is often in association with multiple sclerosis (MS). Proinflammatory cytokines trigger neuronal damage in neuroinflammatory disorders but their role in optic neuritis is poorly investigated.. The objective of this work is to investigate the associations of intrathecal contents of proinflammatory cytokines with transient and persistent dysfunctions after optic neuritis.. In 50 MS patients followed for up to six months, cerebrospinal fluid (CSF) levels of IL-1β, TNF and IL-8 were determined, along with clinical, neurophysiological and morphological measures of optic neuritis severity.. Visual impairment, measured by high- and low-contrast visual acuity, and delayed visual-evoked potential (VEP) latencies were significantly correlated to IL-8 levels during optic neuritis. IL-8 at the time of optic neuritis was also associated with persistent demyelination and final axonal loss, inferred by VEP and optical coherence tomography measures, respectively. Contents of IL-8 were correlated to functional visual outcomes, being higher among patients with incomplete recovery. Multivariate analysis confirmed that IL-8 significantly predicted final visual acuity, at equal values of demographics and baseline visual scores.. Our study points to IL-8 as the main inflammatory cytokine associated with demyelination and secondary neurodegeneration in the optic nerve after optic neuritis.

Topics: Adult; Demyelinating Diseases; Evoked Potentials, Visual; Female; Humans; Interleukin-1beta; Interleukin-8; Male; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Optic Nerve; Optic Neuritis; Tomography, Optical Coherence; Tumor Necrosis Factor-alpha