Vitamin D immunomodulatory potential in multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of unknown etiology whose treatment is of limited efficiency and therefore has a high social burden. As it has been suggested that myelin destruction model, the clinical manifestation and the potential of therapeutic response in MS are correlated, it is quite justifiable that we study various factors (genetic, hormonal, environmental) that take part in the autoimmune process in order to improve the control over the disrupted immune regulation. Results from epidemiological and clinical studies clearly suggest that changes in vitamin D serum concentrations are correlated with the magnitude of the risk of developing MS, the phases of relapse and remittance and with gender differences in vitamin D metabolism. Experimental and clinical studies also have established that 25-hydroxy vitamin D (25(OH)D) and 1,25-dihydroxy vitamin D (1,25(OH)2D) exert an immunomodulatory effect in the central nervous system and peripheral organs of the immune system. The standard reference range of vitamin D concentration in serum is 50-80 nmol/l--it provides normal calcium metabolism. Issues that are discussed include the vitamin D serum concentration needed to suppress the aberrant immune response in MS patients; a subgroup of MS patients suitable for vitamin D treatment, the vitamin D being applied in optimally effective and safe dosage. MS prevalence rate in Bulgaria has increased two-fold in 17 years but this is a rather short interval to be able to assume that the gene pool of the population changes. Thus further studies on possible interactions between different environmental factors and these factors' role in the disease pathogenesis are justified and necessary.

Clinical and laboratory study of pro-inflammatory and antiinflammatory cytokines in women with multiple sclerosis.

UNLABELLED: Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system characterised with a complex system of interactions between proinflammatory and anti-inflammatory cytokines in its course. AIM: The aim of the present study was to investigate the serum levels of cytokines TNF-a, IFN-gamma, IL-4 and IL-10 in female patients with MS and healthy individuals, the changes occurring in the relapse and remission phases of the disease and their correlation with the severity of the neurological deficit. PATIENTS AND METHODS: Thirty-five women with relapsing-remitting MS were examined. The patients' age ranged between 18 and 50 years and MS was verified clinically and by magnetic resonance imaging according to the McDonald criteria. Thirteen of the patients were treated with interferon-beta-1b. The serum concentrations of TNF-a, IFN-y, IL-4 and IL-10 were determined twice - in relapse and in remission - using an enzyme-linked immunosorbent assay (ELISA). The control group consisted of 35 age-matched healthy females. RESULTS: The comparison of cytokine serum concentrations during the two phases of the disease showed significant elevation of the TNF-alpha serum levels in the relapse phase and of IL-4 - in the remission phase. The comparison between the patients and the healthy control subjects demonstrated statistically significant lower concentrations of TNF-a in remission patients and higher concentrations of IL-10 in relapse patients. The patients with interferon-beta-lb treatment showed different profile of cytokine secretion from the patients without interferon-beta-1b treatment. Interferon-beta-1b-treated patients showed significantly lower serum levels of TNF-a and IFN-gamma during the relapse phase and higher TNF-a and IL-10 serum levels during the remission phase compared with the untreated patients. CONCLUSIONS: Serum levels of TNF-a and IL-4 objectively reflect the immune response during relapse and remission of the disease. The severity of neurological deficit as estimated with the expanded disability status scale (EDSS) does not depend on the serum levels of TNF-a, IL-10 and IFN-gamma in the two phases of MS.

Female sex hormones and multiple sclerosis.

Multiple sclerosis is the most frequent debilitating neurological disease in young subjects. The autoimmune process predominantly affects females. This paper presents a review of experimental and clinical data about the effect of female sex hormones and conditions associated with hormonal alterations on the disease process. Specific consideration is given to the use of estrogens as a remedy influencing the disease course. There haven't been enough studies to indicate presence of either hormonal disbalance in females with multiple sclerosis or peculiarities in the hormone-cytokine profile during disease relapse and remission. Further investigations in this area are needed to provide more profound knowledge of the pathogenesis of this socially significant disease.

Female sex hormones and cytokine secretion in women with multiple sclerosis.

UNLABELLED: Data from experimental and clinical research suggest that sex hormones may influence the autoimmune process in multiple sclerosis (MS). Studies on the hormonal profile of patients with MS and its relation to the disease activity provide heterogeneous results. OBJECTIVES: The aim of this study is to investigate the changes in serum levels of estradiol and progesterone and their correlations with the cytokine profile and the degree of disability in women with relapsing-remitting MS (RRMS). METHODS: The serum concentrations of estradiol, progesterone, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukine-4 (IL-4) and interleukine-10 (IL-10) were measured and the degree of disability was determined in 35 women with RRMS, during relapse and remission. Serum levels of hormones were measured by micro-particle enzyme immunoassay and ELISA was used for the cytokines concentrations. The degree of disability was assessed by the Expanded Disability Status Scale and the Scripps Neurological Rating Scale. RESULTS: Sixty per cent of patients had serum concentrations of estradiol and/or progesterone below the lower limit of normal in one or both phases of MS. Hormonal levels increased significantly during remission in these patients. Women with and without hormonal abnormalities differed in terms of cytokine profile during relapse and remission. Significantly higher TNF-alpha in both phases and IFN-gamma in remission was found for the patients with hormonal disturbances compared to these with normal hormonal status. CONCLUSIONS: Our study finds high frequency of hormonal disturbances among female patients with RRMS. Abnormally low concentrations of sex hormones are associated with higher serum levels of TNF-alpha and IFN-gamma, which could suggest suppressive effect of estradiol and progesterone on pro-inflammatory cytokine secretion.