Multiple sclerosis (MS) is the most frequent demyelinating disease of the central nervous system. Peptidases like dipeptidyl peptidase IV (DP IV, CD26) and aminopeptidase N (APN, CD13) play a regulatory role in T cell activation and represent potential targets for the treatment of inflammatory disorders. Synthetic inhibitors of DP IV ...

The role of immune-mediated axonal injury in the induction of nonremitting functional deficits associated with multiple sclerosis is an area of active research that promises to substantially alter our understanding of the pathogenesis of this disease and modify or change our therapeutic focus. This review summarizes the current state of ...

Multiple sclerosis (MS) is a progressive, presumably autoimmune, degenerative disease of the central nervous system (CNS). The mechanisms which trigger the disease are unknown, but the pathology of MS is caused by the host's own immune system, which invades the CNS and attacks the myelin sheath that protects and insulates ...

The role of T regulatory (Treg) cells expressing the forkhead box transcription factor 3 (foxp3) in the control of autoaggressive immune responses is the subject of intense investigation. Here we explore the contribution of these cells to the regulation of experimental autoimmune encephalomyelitis (EAE). Starting from a historical perspective, we ...

OBJECTIVES: Pediatric-onset multiple sclerosis offers a unique window into early targets and mechanisms of immune dysregulation. It is unknown whether heightened T-cell reactivities documented in adult patients, to both target-organ and environmental antigens, emerge in parallel or develop as early or late events. Our objectives were to determine the presence, ...

Statins' recently discovered anti-inflammatory effects place them at the forefront of the new therapies for chronic inflammatory and autoimmune diseases. Our recent study demonstrated that simvastatin exerts an independent immunomodulatory effect on the human monocytes and CD4+ cells. In addition to the statin-mediated effect on the monocyte cytokine production, which ...

T-cell vaccination (TCV) is a unique approach to induce immune regulation that may have importance in the treatment of autoimmune diseases, including multiple sclerosis (MS). TCV employs a classic vaccine strategy of injecting an attenuated form of the disease-causing agent--in this case, myelin-reactive T cells--that have been selected and expanded ...

Multiple sclerosis (MS) is a neurological disorder of the central nervous system characterized by demyelination and neurodegeneration. Although the pathogenesis of MS is not completely understood, various studies suggest that immune-mediated loss of myelin and mitochondrial dysfunction are associated with the disease. Mitochondria are one of the main cellular sources ...

Multiple sclerosis (MS) is a major inflammatory and demyelinating disease of the central nervous system and has an increasing prevalence in populations residing at higher latitudes. This observation may indicate a protective effect of sunlight exposure, which is reduced at higher latitudes and may contribute to insufficient levels of vitamin ...

OBJECT: Inhibition of remyelination is part of the complex problem of persistent dysfunction after spinal cord injury (SCI), and residual myelin debris may be a factor that inhibits remyelination. Phagocytosis by microglial cells and by macrophages that migrate from blood vessels plays a major role in the clearance of myelin ...

Considerable research has been devoted to the role of the adaptive immune system in the pathogenesis of autoimmune inflammatory demyelination (AID). AID is thought to occur spontaneously in patients with multiple sclerosis (MS), a common cause of neurological disability. AID is also observed in the best characterized animal model of ...

Recombinant T cell receptor (TCR) ligands (RTL) represent the minimal interactive surface with antigen-specific T cell receptors. These novel constructs fold similarly to native four-domain MHC/peptide complexes but deliver suboptimal and qualitatively different signals that cause a 'cytokine switch' to anti-inflammatory factors in targeted encephalitogenic T cells. RTL treatment can ...

Most of the conventional immunosuppressive drugs act by inhibiting the activation of enzymes, production of cytokines or proliferation of immune cells. Recently much attention is given to a new class of inhibitors that act by counteracting the functions of the lysophospholid sphingosine-1-phosphate (S1P). S1P is emerging as a potent stimulator ...

BACKGROUND: Leukotriene B4 (LTB4) is a potent inflammatory mediator that also stimulates the immune response. In addition, it promotes polymorphonuclear leukocyte phagocytosis, chemotaxis, chemokinesis and modulates cytokines release. Regarding chemical instability of the leukotriene molecule, in the present study we assessed the immunomodulatory activities conferred by LTB4 released from microspheres ...

BACKGROUND: Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component. It has been suggested that novel treatment options are needed that target both aspects of the disease. Evidence from basic and clinical studies suggests that testosterone has an immunomodulatory as well as ...

In multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE), impairment of glial "Excitatory Amino Acid Transporters" (EAATs) together with an excess glutamate-release by invading immune cells causes excitotoxic damage of the central nervous system (CNS). In order to identify pathways to dampen excitotoxic inflammatory CNS damage, we ...

BACKGROUND: Kinins are important mediators of inflammation and act through stimulation of two receptor subtypes, B1 and B2. Leukocyte infiltration contributes to the pathogenesis of autoimmune inflammation in the central nervous system (CNS), occurring not only in multiple sclerosis (MS) but also in experimental autoimmune encephalomyelitis (EAE). We have previously ...

An array of studies implicate different classes of protease and their endogenous inhibitors in multiple sclerosis (MS) pathogenesis based on expression patterns in MS lesions, sera, and/or cerebrospinal fluid (CSF). Growing evidence exists regarding their mechanistic roles in inflammatory and neurodegenerative aspects of this disease. Proteolytic events participate in demyelination, ...

Derivative myelin associated glycoprotein (dMAG) results from proteolysis of transmembrane MAG and can inhibit axonal growth. We have tested the ability of certain matrix metalloproteinases (MMPs) elevated with inflammatory and demyelinating diseases to cleave MAG. We show MMP-2, MMP-7 and MMP-9, but not MMP-1, cleave recombinant human MAG. Cleavage by ...

In multiple sclerosis (MS) and its widely accepted animal model, experimental autoimmune encephalomyelitis (EAE), the failure of autoreactive immune cells to undergo apoptosis is thought to contribute to CNS tissue damage and disease progression. Promoting apoptosis of myelin-reactive immune cells in diseases such as MS, may delay disease progression and ...

PURPOSE OF REVIEW: Systemic sclerosis is a complex disease characterized by immune/inflammatory, vascular and fibrotic processes. To date, no treatment has proven effective in modifying the course of the disease. Recent studies have begun to yield insights into the nature and interrelationship among these processes, and their cellular and molecular ...

In multiple sclerosis (MS), myelin destroyed by the immune attack is not effectively repaired by oligodendrocytes (OLs) and MS foci eventually undergo glial scarring. Although oligodendrocyte precursor cells (OPCs) are normally recruited to the lesion areas, they fail to mature and remyelinate the damaged fibers. Activation of the Notch pathway ...

Hyperforin (Hyp) is an active compound contained in the extract of Hypericum perforatum, well known for its antidepressant activity. However, Hyp has been found to possess several other biological properties, including inhibitory effects on tumor invasion, angiogenesis, and inflammation. In this paper, we show that treatment with Hyp inhibited IFN-gamma ...

Innate immune cells may regulate adaptive immunity by balancing different lineages of T cells and providing negative costimulation. In addition, CD11b(+)Gr-1(+) myeloid-derived suppressor cells have been described in tumor, parasite infection, and severe trauma models. In this study, we observe that splenic CD11b(+) cells markedly increase after experimental autoimmune encephalomyelitis ...

This review examines the mode of action, safety profile and clinical efficacy of some of the most promising new therapeutic strategies for multiple sclerosis. Autologous hematopoietic stem cell transplantation can regenerate a new and tolerant immune system and is a potentially effective rescue therapy in a subset of patients with ...

We investigated whether monocyte-derived dendritic cells (MDDCs) generated in vitro from bacteria-infected MS patients modified autoreactive T cells activation patterns. T cell clones (TCCs) stimulated with MDDCs from infected MS patients responded with maximal proliferation, inducing IL-12, IL-17 and IFN-gamma secretion, at concentrations significantly lower than after incubation with MDDCs ...

Silibinin is the major pharmacologically active compound of silymarin, the Silybum marianum fruit extract. Hepatoprotective activities of silibinin/silymarin are well-known, and recent studies demonstrated their anti-inflammatory and anti-carcinogenic effects which are due to inhibition of the transcription factor NF-kappaB. Based on this knowledge, we hypothesized that silibinin could be effective ...

The pathogenesis of experimental autoimmune encephalomyelitis (EAE) can be efficiently kept under control by specialized subsets of CD4+ T lymphocytes able to negatively regulate the function of T cells with encephalitogenic potential. A number of observations support a role for such suppressor T cells in controlling early phases of disease ...

The cannabis plant (Cannabis sativa) has been known by many names but the question remains 'Can we call it medicine?' There has been renewed interest in the value of cannabis for the control of neuroinflammatory conditions such as multiple sclerosis, where it has been shown to have some effect on ...

The establishment of new hygienic conditions plays a role in the appearance of autoimmunity in "westernalised" countries. Consistently, but still unconvincingly, several epidemiological and immunogenetic evidences link the disappearance of malaria with the increase of multiple sclerosis (MS) in Sardinia, insular Italy. To this purpose, we have made an attempt ...

Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found in plant products, including red grapes, exhibits anticancer, antioxidant, and anti-inflammatory properties. Using an animal model of multiple sclerosis (MS), we investigated the use of resveratrol for the treatment of autoimmune diseases. We observed that resveratrol treatment decreased the clinical symptoms and inflammatory responses ...

In Theiler's murine encephalomyelitis virus (TMEV) infection, an animal model for multiple sclerosis (MS), axonal injury precedes inflammatory demyelinating lesions, and the distribution of axonal damage present during the early phase of infection corresponds to regions where subsequent demyelination occurs during the chronic phase. We hypothesized that axonal damage recruits ...

CCL19 and CCL21 bind to CCR7, which is crucial for both inducing an immune response and establishing immunological tolerance. We report that in the normal human brain CCL19, but not CCL21, is transcribed, and detectable as a protein in tissue lysates and in cerebrospinal fluid. In both active and inactive ...

Myelination is critical for the normal functioning of the vertebrate nervous system. In the CNS, myelin is produced by oligodendrocytes, and the loss of oligodendrocytes and myelin results in severe functional impairment. Although spontaneous remyelination occurs in chronic demyelinating diseases such as multiple sclerosis, the repair process eventually fails, often ...

Understanding of autoimmune diseases, including multiple sclerosis, has expanded considerably in recent years. New insights have been provided by not only animal models but also studies of patients, often in conjunction with experimental therapies. It is accepted that autoimmune T cells mediate the early steps of new multiple sclerosis lesions, ...

Regions of myelinated normal-appearing white matter in clinically early cases of MS show activated parenchymal microglia, with evidence of the beginnings of endocytosis and lysis of the myelin sheath. Whether these cells act as scavengers and restorers of already-damaged tissue, or play an essential primary and aggressive role in myelin ...

Excessive or inappropriate production of IL-17A has been reported in diseases such as rheumatoid arthritis, asthma, and multiple sclerosis. The potential clinical relevance of these correlations was suggested by the protective effects of anti-IL-17A monoclonal antibodies in various mouse disease models. However, the chronic nature of the corresponding human afflictions ...

IL-27 has been shown to play a suppressive role in experimental autoimmune encephalomyelitis (EAE) as demonstrated by more severe disease in IL-27R-deficient (WSX-1(-/-)) mice. However, whether IL-27 influences the induction or effector phase of EAE is unknown. This is an important question as therapies for autoimmune diseases are generally started ...

The primary pathogenetic mechanism responsible for the distinctive demyelinating lesions in the Central Nervous System (CNS) in Multiple Sclerosis (MS), first described in remarkable detail by Charcot more than 170 years ago, remains one of the most baffling conundrums in medicine. A possible role for bacterial cell molecules and transportable ...

Multiple sclerosis (MS) is a complex neurodegenerative disease whose pathogenesis involves genetic and environmental risk factors leading to an aberrant, neuroantigen-specific, CD4+ T cell-mediated autoimmune response. In support of the hypothesis that vitamin D3 may reduce MS risk and severity, we found that vitamin D3 and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) inhibited ...

Myelination in the nervous system is a tightly regulated process that is mediated by both soluble and non-soluble factors acting on axons and glial cells. This process is bi-directional and involves a variety of neurotrophic and gliotrophic factors acting in paracrine and autocrine manners. Neuron-derived trophic factors play an important ...

It is obvious that the central nervous system plays a role in the regulation of an immune response. However, the mechanisms of this regulation are poorly understood. The goal of the present study was to examine the role of one of the neurotransmitters - dopamine, in this process. We used ...

Axonal damage and loss of neurons correlate with permanent vision loss and neurologic disability in patients with optic neuritis and multiple sclerosis (MS). Current therapies involve immunomodulation, with limited effects on neuronal damage. The authors examined potential neuroprotective effects in optic neuritis by SRT647 and SRT501, two structurally and mechanistically ...

CD4(+)CD25(+) regulatory T cells (Tregs) are potent immunosuppressors that are pivotal in the maintenance of self-tolerance. The involvement of Tregs in therapies for immune-mediated diseases has been proposed, but direct supporting evidence is still lacking. While investigating mechanisms underlying the clinical benefits of glatiramer acetate (GA) in an animal model ...

Multiple sclerosis (MS) is thought to be an autoimmune disease in which activated T-cells initiate a macrophage mediated destruction of CNS myelin. Bone marrow transplantation (BMT) is currently being evaluated in the treatment of MS in patients with aggressive disease activity. Autologous BMT could potentially reset the immune response to ...

Multiple sclerosis (MS), the most common nontraumatic cause of neurologic disability in young adults in economically developed countries, is characterized by inflammation, gliosis, demyelination, and neuronal degeneration in the CNS. Bone marrow transplantation (BMT) can suppress inflammatory disease in a majority of patients with MS but retards clinical progression only ...

Multiple sclerosis is a heterogeneous disease associated with a rupture of immunological tolerance toward CNS antigens in both T- and B-lymphocyte compartments. The association of human leukocyte antigen genes with higher susceptibility to multiple sclerosis, and the capacity of immune-modulating drugs that block leukocyte transit into the CNS (e.g., natalizumab) ...

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an immune-mediated disorder characterized by progressive or relapsing symmetrical motor or sensory symptoms and signs in more than one limb, developing over at least 2 months. It may cause prolonged periods of disability and even death. Evidence from trials suggests that plasma exchange provides ...

Fatty acid-binding proteins (FABPs) act as intracellular receptors for a variety of hydrophobic compounds, enabling their diffusion within the cytoplasmic compartment. Recent studies have demonstrated the ability of FABPs to simultaneously regulate metabolic and inflammatory pathways. We investigated the role of adipocyte FABP and epithelial FABP in the development of ...

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) leading to demyelination, axonal damage, and progressive neurologic disability. The development of MS is influenced by environmental factors, particularly the Epstein-Barr virus (EBV), and genetic factors, which include specific HLA types, particularly DRB1*1501-DQA1*0102-DQB1*0602, and a predisposition to ...