Cytokines and disability in interferon-ß-1b treated and untreated women with multiple sclerosis.

BACKGROUND AND AIMS: T-helper (Th) cells involved in the pathogenesis of multiple sclerosis (MS) represent a functionally heterogeneous population defined by their cytokine secretion profile. The effects of immunotherapeutic drugs on the cytokine network are still not fully clarified. This study aimed to investigate serum levels of IFN-γ, TNF-α, IL-4, IL-10 in interferon-ß-1b-treated and untreated women with relapsing-remitting MS (RRMS) in comparison with healthy controls and the relationship between cytokine concentrations and the degree of disability. METHODS: The study included 35 women with RRMS and 35 age-matched healthy controls. The patients were divided in two groups: Group A-without disease modifying treatment; Group B-treated with interferon-ß-1b. Degree of disability was assessed by the Expanded Disability Status Scale (EDSS). Serum cytokine concentrations were measured by ELISA during relapse and remission. RESULTS: Group A showed higher IFN-γ in remission (p = 0.0239) than the controls; Group B had lower IFN-γ during relapse (p = 0.0226) than controls. EDSS in relapse correlated with the levels of IL-10 for Group A (p = 0.015) and with the concentration of IFN-γ for Group B (p = 0.039). Nontreated patients showed higher EDSS in relapse compared to the interferon-ß-1b-treated group (p = 0.005). CONCLUSIONS: We found an imbalance in the patients' cytokine profile, which may be seen as supportive of the hypothesis that demyelination in the central nervous system is mediated by Th1 lymphocytes. IFN-γ is probably one of the important indicators for intensity of the immune reaction and shows promise as a potential biomarker for the therapeutic effect of interferon-ß-1b. The role of IL-10 in the autoimmune process needs further investigation.

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.