Effects of IFN-ß1a and IFN-ß1b treatment on the expression of cytokines, inducible NOS (NOS type II), and myelin proteins in animal model of multiple sclerosis.

The aim of this study was to investigate the effects of interferon (IFN)-ß1a and IFN-ß1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the Lewis rat experimental autoimmune encephalomyelitis (EAE), animal model of multiple sclerosis. To induce EAE, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in Freund's complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an emulsion and additionally 4-mg/ml Mycobacterium tuberculosis (H37Ra). The rats were treated three times per week with subcutaneous applications of 300,000 units IFN-ß1a or IFN-ß1b. The treatments were started 8 days prior to immunization and continued until day 14 after immunization. The rats were killed on the 14th day of the experiment. EAE induced dramatic increase in interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-concentrations and inducible nitric oxide synthase (iNOS) expression in the brain, which closely corresponded to the course of neurological symptoms and the loss of weight. Both IFN-ß1b and IFN-ß1a treatments inhibited the pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α and IFN-γ), decreased the activation of astrocytes, increased the myelin protein level in the brain cortex, and improved the neurological status of EAE rats by different mechanisms; IFN-ß1a reduced iNOS expression, at least in part, by the enhancement of IL-10, while IFN-ß1b diminished IL-10 concentration and did not decrease EAE-induced iNOS expression.

Adipose-Derived Cells (Stromal Vascular Fraction) Transplanted for Orthopedical or Neurological Purposes: Are They Safe Enough?

Although mesenchymal stem cells are used in numerous clinical trials, the safety of their application is still a matter of concern. We have analysed the clinical results of the autologous adipose-derived stem cell treatment (stromal vascular fraction (SVF) containing adipose-derived stem cells, endothelial progenitors, and blood mononuclear cells) for orthopedic (cartilage, bone, tendon, or combined joint injuries) and neurologic (multiple sclerosis) diseases. Methods of adipose tissue collection, cell isolation and purification, and resulting cell numbers, viability, and morphology were considered, and patient's age, sex, disease type, and method of cell administration (cell numbers per single application, treatment numbers and frequency, and methods of cell implantation) were analysed and searched for the unwanted clinical effects. Results of cellular therapy were compared retrospectively to those obtained with conventional medication without SVF application. SVF transplantation was always the accessory treatment of patients receiving "standard routine" therapies of their diseases. Clinical experiments were approved by the Bioethical Medical Committees supervising the centers where patients were hospitalised. The conclusion of the study is that none of the treated patients developed any serious adverse event, and autologous mesenchymal stem (stromal) cell clinical application is a safe procedure resulting in some beneficial clinical effects (not analysed in this study).

[Current state of research on multiple sclerosis]. / Aktualny stan badan nad stwardnieniem rozsianym.

Multiple sclerosis (MS) is a chronic disease of the central nervous system (CNS) autoimmune. It belongs to a group of demyelinating disease, which is an irreversible consequence of disability. Epidemiological data indicate that occurs in nearly 2.5 million people around the world. Despite much research is still little known about the disease pathomechanism. Do not we also have so far fully effective the treatment. Available immunomodulatory drugs offer new opportunities defer progression for years. Both fingolimod and natalizumab are more effective in the treatment of MS than the widely used IFN-beta and glatiramer acetate (GA). However, new drugs pose a greater risk of side effects than first-generation drugs. The rapid development of research offers the prospect of a better understanding of the pathogenesis of the disease and to develop more effective treatments.

Effects of interferon ß-1a and interferon ß-1b monotherapies on selected serum cytokines and nitrite levels in patients with relapsing-remitting multiple sclerosis: a 3-year longitudinal study.

OBJECTIVE: Interferon (IFN)ß treatment is a mainstay of relapsing-remitting multiple sclerosis (RRMS) immunotherapy. Its efficacy is supposedly a consequence of impaired trafficking of inflammatory cells into the central nervous system and modification of the proinflammatory/antiinflammatory cytokine balance. However, the effects of long-term monotherapy using various IFNß preparations on cytokine profiles and the relevance of these effects for the therapy outcome have not yet been elucidated. METHODS: Changes were compared in serum levels of TNFα, IFNγ, interleukin (IL)-6, IL-10 and nitrite between RRMS patients given 3-year treatment with intramuscular IFNß-1a (30 µg once a week) or subcutaneous IFNß-1b (250 µg every other day). Only the data from patients who completed the 3-year study (n = 20 and n = 18, respectively) were analyzed. RESULTS: Three-year IFNß-1a or IFNß-1b monotherapy reduced serum nitrite levels by 77 and 71%, respectively, lowered multiple sclerosis relapse annual rate by 70 and 71%, respectively, and significantly and similarly lowered Expanded Disability Status Scale scores in both study groups (by 0.9 on average). The two monotherapies showed little if any effect on cytokine levels and cytokine level ratios after the first year, but exerted diverging effects on these indices later on; the only exception was the IFNγ/IL-6 ratio that showed a monotonous rise in both study groups over the entire study period. CONCLUSION: During long-term IFNß monotherapy, the levels of the studied cytokines show no relevance to the course of RRMS and neurological status of patients, whereas there seems to be a link between these clinical indices and the activity of nitric oxide-mediated pathways.