The initiation and prevention of multiple sclerosis.
ABSTRACT Although strong genetic determinants of multiple sclerosis (MS) exist, the findings of migration studies support a role for environmental factors in this disease. Through rigorous epidemiological investigation, Epstein-Barr virus infection, vitamin D nutrition and cigarette smoking have been identified as likely causal factors in MS. In this Review, the strength of this evidence is discussed, as well as the potential biological mechanisms underlying the associations between MS and environmental, lifestyle and dietary factors. Both vitamin D nutrition and cigarette smoking are modifiable; as such, increasing vitamin D levels and smoking avoidance have the potential to substantially reduce MS risk and influence disease progression. Improving our understanding of the environmental factors involved in MS will lead to new and more-effective approaches to prevent this disease.
- SourceAvailable from: Rocco Rossano[Show abstract] [Hide abstract]
ABSTRACT: The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness. © The Author(s) 2015.ASN Neuro 02/2015; 7(1). DOI:10.1177/1759091414568185 · 4.44 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The present study aimed at profiling inflammatory cytokines for neurological and psychiatric diseases. A total of 86 patients with meningitis, multiple sclerosis, tension-type headache, idiopathic facial nerve palsy (IFNP), affective and schizophrenic disorders were tested for both, serum and cerebrospinal fluid (CSF) using a multiplexed cytokine ELISA for IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-5, IL-8/CXCL8, IL-10, IL12p70, IL-13 and IL-17. Cases with viral and bacterial meningitis had unequivocally higher cytokine concentrations in the CSF when compared with serum. Bacterial meningitis was unique by extremely elevated IL-17, TNF-α and IL-1β, indicating a plethora of inflammatory pathways, selectively activated in the CSF. In relapsing multiple sclerosis, IFN-γ and IL-10 were elevated in both, serum and CSF, but IL-12p70, IL-5, IL-13, and TNF-α were more prominent in serum than in CSF. Qualitatively similar biomarker patterns were detected in patients with idiopathic facial nerve palsy and tension-type cephalgia. Affective and schizophrenic disorders clearly present with an inflammatory phenotype in the CSF and also serum, the cytokines determined were in general higher in schizophrenia. Except IFN-γ, schizophrenic patients had higher IL-12p70 and a trend of higher IL-10 and IL-13 in serum suggesting a more prominent TH2-type counter regulatory immune response than in affective disorders. These differences were also mirrored in the CSF. Elevated IL-8 appears to be the most sensitive marker for inflammation in the CSF of all diseases studied, whereas TNF-α was restricted to peripheral blood. With the exception of IL-8, all but viral and bacterial meningitis, studied, displayed higher means of elevated lymphokine concentrations in the serum than in the CSF. This observation supports the concept of immunological crosstalk between periphery and intrathecal immunity in neurological and psychiatric diseases.Cytokine 09/2014; 69(1):62–67. DOI:10.1016/j.cyto.2014.05.008 · 2.87 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Mycobacterium avium ss. paratuberculosis (MAP) is an intracellular pathogen recently associated with multiple sclerosis (MS). Aiming to identify immunodominant epitopes belonging to MS related protein MAP2694 (UniProt accession no. Q73WG6), we investigated the binding activity of selected peptides against MS Sardinian sera. An overlapping 9-mers peptide library was synthesized spanning the entire aminoacidic sequence of the protein. Peripheral blood was collected from 47 MS patients and 42 sex and age matched healthy volunteers and subjected to enzyme-linked immunosorbent assay (ELISA) in order to investigate the reaction against the linear peptides generated. Two out of 58 synthetic 9-mers were strongly recognized by MS patients' antibodies compared to controls. A competitive inhibition assay demonstrated that these two epitopes are immunodominant antibody targets within MAP2694 protein, as sera pre-adsorbed with these peptides were able to significantly block the antibody reaction to the MAP2694 protein, even if at a lesser extent than MAP2694 protein itself.Molecular Immunology 09/2013; 57(2):138-140. DOI:10.1016/j.molimm.2013.09.001 · 3.00 Impact Factor