Explore the vast range of titles available.

Myelin-oligodendrocyte glycoprotein antibody associated disease (MOGAD) is a common inflammatory disease of the central nervous system (CNS) in children that can lead to demyelination. Evaluation and monitoring of biomarkers associated with its pathogenesis would provide vital information on disease progression and therapeutic assessment. We assessed NLRP3, HMGB1, IL-6, and IL-33 levels in the cerebrospinal fluid (CSF) of pediatric patients with MOGAD at different time points and their association with the risk of disease. We recruited 30 patients with MOGAD (20 in the acute phase and 10 in remission) and 10 control patients with noninflammatory demyelinating disease. The expanded disability status scale (EDSS) was used to assess disease severity. NLRP3, HMGB1, and IL-6 levels in the CSF were significantly higher in patients with MOGAD during the acute phase than in remission ( < 0.05, < 0.05, < 0.05) and the control group ( < 0.01, < 0.0001, < 0.01). HMGB1 levels were significantly correlated with NLRP3 levels ( < 0.01) during the acute phase. Moreover, we found notable correlation between HMGB1 levels and EDSS ( < 0.05) scores. IL-6 levels were significantly correlated with the total number of attacks ( < 0.05), but not with EDSS scores. These findings suggest that NLRP3, HMGB1, and IL-6 in the CSF may be potential therapeutic targets and are at least partly involved in the pathogenesis of pediatric MOGAD. HMGB1 in the CSF may be a potential biomarker correlating with pediatric MOGAD severity. Further investigations are warranted to validate potential cytokine pathways between that NLRP3, HMGB1, and IL-6 of MOGAD.

It is of great interest to understand how invading pathogens are sensed within the brain, a tissue with unique challenges to mounting an immune response. The eukaryotic parasite Toxoplasma gondii colonizes the brain of its hosts, and initiates robust immune cell recruitment, but little is known about pattern recognition of T . gondii within brain tissue. The host damage signal IL-33 is one protein that has been implicated in control of chronic T . gondii infection, but, like many other pattern recognition pathways, IL-33 can signal peripherally, and the specific impact of IL-33 signaling within the brain is unclear. Here, we show that IL-33 is expressed by oligodendrocytes and astrocytes during T . gondii infection, is released locally into the cerebrospinal fluid of T . gondii -infected animals, and is required for control of infection. IL-33 signaling promotes chemokine expression within brain tissue and is required for the recruitment and/or maintenance of blood-derived anti-parasitic immune cells, including proliferating, IFN-γ-expressing T cells and iNOS-expressing monocytes. Importantly, we find that the beneficial effects of IL-33 during chronic infection are not a result of signaling on infiltrating immune cells, but rather on radio-resistant responders, and specifically, astrocytes. Mice with IL-33 receptor-deficient astrocytes fail to mount an adequate adaptive immune response in the CNS to control parasite burden–demonstrating, genetically, that astrocytes can directly respond to IL-33 in vivo . Together, these results indicate a brain-specific mechanism by which IL-33 is released locally, and sensed locally, to engage the peripheral immune system in controlling a pathogen.

Multiple sclerosis is a disabling inflammatory disorder of the central nervous system characterized by demyelination and neurodegeneration. Given that multiple sclerosis remains an incurable disease, the management of MS predominantly focuses on reducing relapses and decelerating the progression of both physical and cognitive decline. The continuous autoimmune process modulated by cytokines seems to be a vital contributing factor to the development and relapse of multiple sclerosis. This review sought to summarize the role of selected interleukins in the pathogenesis and advancement of MS. Patients with MS in the active disease phase seem to exhibit an increased serum level of IL-2, IL-4, IL-6, IL-13, IL-17, IL-21, IL-22 and IL-33 compared to healthy controls and patients in remission, while IL-10 appears to have a beneficial impact in preventing the progression of the disease. Despite being usually associated with proinflammatory activity, several studies have additionally recognized a neuroprotective role of IL-13, IL-22 and IL-33. Moreover, selected gene polymorphisms of IL-2R, IL-4, IL-6, IL-13 and IL-22 were identified as a possible risk factor related to MS development. Treatment strategies of multiple sclerosis that either target or utilize these cytokines seem rather promising, but more comprehensive research is necessary to gain a clearer understanding of how these cytokines precisely affect MS development and progression.

Background Interleukin-33 is a cytokine endowed with pro- and anti-inflammatory properties that plays a still poorly defined role in the pathogenesis of a number of central nervous system (CNS) conditions including Alzheimer’s disease (AD). We analyzed this cytokine and its decoy receptor sST2 in Alzheimer’s disease (AD) and mild cognitive impairment (MCI). Method IL-33 and sST2 were analyzed in serum and CSF of AD and MCI patients, comparing the results to those obtained in age-matched healthy controls (HC). Because of the ambiguous role of IL-33 in inflammation, the concentration of both inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokines was analyzed as well in serum and cerebrospinal fluid (CSF) of the same individuals. Finally, the effect of IL-33 on in vitro Aβ 42 -stimulated monocytes of AD, MCI, and HC individuals was examined. Results As compared to HC, (1) IL-33 was significantly decreased in serum and CSF of AD and MCI, (2) sST2 was increased in serum of AD and MCI but was undetectable in CSF, (3) serum and CSF IL-1β concentration was significantly increased and that of IL-10 was reduced in AD and MCI, whereas no differences were observed in IL-6. In vitro addition of IL-33 to LPS+Aβ 42 -stimulated monocytes downregulated IL-1β generation in MCI and HC, but not in AD, and stimulated IL-10 production in HC alone. IL-33 addition also resulted in a significant reduction of NF-kB nuclear translocation in LPS+Aβ 42 -stimulated monocytes of HC alone. Conclusions These data support the hypothesis that IL-33 plays a complex anti-inflammatory role that is lost in AD- and MCI-associated neuroinflammation; results herein also suggest a possible use of IL-33 as a novel therapeutic approach in AD and MCI.

Abstract Chronic obstructive pulmonary disease (COPD) is a worldwide threat. Cigarette smoke (CS) exposure causes cardiopulmonary disease and COPD and increases the risk for pulmonary tumors. In addition to poor lung function, patients with COPD are susceptible to bouts of dangerous inflammation triggered by pollutants or infection. These severe inflammatory episodes can lead to additional exacerbations, hospitalization, further deterioration of lung function, and reduced survival. Suitable models of the inflammatory conditions associated with CS, which potentiate the downward spiral in patients with COPD, are lacking, and the underlying mechanisms that trigger exacerbations are not well understood. Although initial CS exposure activates a protective role for vascular endothelial growth factor (VEGF) functions in barrier integrity, chronic exposure depletes the pulmonary VEGF guard function in severe COPD. Thus, we hypothesized that mice with compromised VEGF production and challenged with CS would trigger human-like severe inflammatory progression of COPD. In this model, we discovered that CS exposure promotes an amplified IL-33 cytokine response and severe disease progression. Our VEGF-knockout model combined with CS recapitulates severe COPD with an influx of IL-33–expressing macrophages and neutrophils. Normally, IL-33 is quickly inactivated by a post-translational disulfide bond formation. Our results reveal that BAL fluid from the CS-exposed, VEGF-deficient cohort promotes a significantly prolonged lifetime of active proinflammatory IL-33. Taken together, our data demonstrate that with the loss of a VEGF-mediated protective barrier, the CS response switches from a localized danger to an uncontrolled long-term and long-range, amplified, IL-33–mediated inflammatory response that ultimately destroys lung function.

Neurological involvement in Behcet's disease (BD), namely, neuro-Behcet's disease (NBD), causes devastating central nervous system (CNS) complications and is present in 5% to 30% of patients with BD.[1] Immunological and molecular pathways are involved in NBD and include the release of interleukin (IL)-1, -6 and -8, and TNF- alpha and IFN- gamma into cerebrospinal fluid (CSF),[2] which reflects a nonspecific inflammatory pattern that is compatible with auto-inflammatory disease pathways. IL-33 is an imconventional member of the IL-1 family that has been recently implicated in several inflammatory and autoimmune diseases. We document here, for the first time, that IL-33 is upregulated in the CNS of patients with NBD.

The administration of interleukin 33 and deletion of IL-33 receptor, ST2 molecule, affects the induction of autoimmunity in different experimental models of human autoimmune diseases. The aim of this study was to analyze the effect of ST2 deletion on the induction of experimental autoimmune encephalomyelitis (EAE) in resistant BALB/c mice. Mice were immunized with MOG(35-55) peptide or disease was induced by passive transfer of encephalitogenic singenic cells and EAE was clinically and histologically evaluated. Expression of intracellular inflammatory cytokines, markers of activation and chemokine receptors on lymphoid tissue and CNS infiltrating mononuclear cells was analyzed by flow cytometry. We report here that deletion of ST2(-/-) molecule abrogates resistance of BALB/c mice to EAE induction based on clinical and histopathological findings. Brain and spinal cord infiltrates of ST2(-/-) mice had significantly higher number of CD4(+) T lymphocytes containing inflammatory cytokines compared to BALB/c WT mice. Adoptive transfer of ST2(-/-) primed lymphocytes induced clinical signs of the disease in ST2(-/-) as well as in WT mice. MOG(35-55) restimulated ST2(-/-) CD4(+) cells as well as ex vivo analyzed lymph node cells had higher expression of T-bet and IL-17, IFN-γ, TNF-α and GM-CSF in comparison with WT CD4(+) cells. ST2(-/-) mice had higher percentages of CD4(+) cells expressing chemokine receptors important for migration to CNS in comparison with WT CD4(+) cells. Draining lymph nodes of ST2(-/-) mice contained higher percentage of CD11c(+)CD11b(+)CD8(-) cells containing inflammatory cytokines IL-6 and IL-12 with higher expression of activation markers. Transfer of ST2(-/-) but not WT dendritic cells induced EAE in MOG(35-55) immunized WT mice. Our results indicate that ST2 deficiency attenuates inherent resistance of BALB/c mice to EAE induction by enhancing differentiation of proinflammatory antigen presenting cells and consecutive differentiation of encephalitogenic T cells in the draining lymph node rather than affecting their action in the target tissue.