thymic-factor--circulating and Multiple-Sclerosis

We carried out a randomized, double-blind, placebo-controlled trial of Nonathymulin (NT, synthetic serum thymic factor) in patients with evolutive multiple sclerosis (MS) and moderate disability. Forty matched patients were treated with subcutaneous NT or placebo for 6 months and followed for another 6 months. There was no significant difference in treatment and control groups in the Kurtzke. Disability scores, Ambulation Index and Functional Scale. No significant side effects were recorded. NT is not effective in treating evolutive and moderately disabled MS.

Topics: Adult; Double-Blind Method; Female; Humans; Male; Middle Aged; Multiple Sclerosis; Thymic Factor, Circulating; Thymus Hormones

This study aimed to assess the effects of the immunomodulator thymulin, a thymic peptide with anti-inflammatory effects, and peroxiredoxin 6 (Prdx6), an antioxidant enzyme with dual peroxidase and phospholipase A2 activities, on the blood‒brain barrier (BBB) condition and general health status of animals with relapsing-remitting experimental autoimmune encephalomyelitis (EAE), which is a model of multiple sclerosis in humans. Both thymulin and Prdx6 significantly improved the condition of the BBB, which was impaired by EAE induction, as measured by Evans blue dye accumulation, tight-junction protein loss in brain tissue, and lymphocyte infiltration through the BBB. The effect was associated with significant amelioration of EAE symptoms. Thymulin treatment was accompanied by a decrease in immune cell activation as judged by interleukin-6, -17, and interferon-gamma cytokine levels in serum and NF-kappaB cascade activation in splenocytes of mice with EAE. Prdx6 did not induce significant immunomodulatory effects but abruptly decreased EAE-induced NOX1 and NOX4 gene expression in brain tissue, which may be one of the possible mechanisms of its beneficial effects on BBB conditions and health status. The simultaneous administration of thymulin and Prdx6 resulted in complete symptomatic restoration of mice with EAE. The results demonstrate prospective strategies for multiple sclerosis treatment.

Topics: Animals; Blood-Brain Barrier; Encephalomyelitis, Autoimmune, Experimental; Humans; Mice; Models, Theoretical; Multiple Sclerosis; Peroxiredoxin VI; Prospective Studies; Thymic Factor, Circulating

Modulation of autoimmune inflammation by the thymic peptides thymulin and thymopentin was studied in mice with acute experimental autoimmune encephalomyelitis (EAE), which resembles multiple sclerosis in humans. EAE was induced in NZW mice by a single immunisation with myelin basic protein coupled with adjuvants. Visible signs of pathology appeared on days 12-14 after the immunisation, peaked on days 20-25, were retained up to day 45, and then reverted. A biphasic cytokine response was also detected. In the "early" phase, which started at day 35, increased levels of interferon-gamma and interleukin-6 in the blood were observed; during the "delayed" phase, which started at day 48, the levels of plasma interleukin-17 and tumour necrosis factor-alpha were also raised. In addition, the phosphorylation of NF-kappaB signalling proteins and the production of heat shock protein Hsp72 were significantly increased in splenic lymphocytes from EAE-bearing mice. When applied intraperitoneally every other day for 30 days, either thymulin or thymopentin (15 μg per 100g of body weight) significantly reduced the disease severity compared to untreated EAE mice. The effect of thymulin but not thymopentin remained after its withdrawal. Thymulin reduced the cytokine response in both the early and the delayed phases, whereas thymopentin only reduced the "early phase cytokines" (IL-6 and interferon-gamma). Both peptides significantly reduced the level of phosphorylation of the NF-kappaB signalling protein IKK and the production of Hsp72 protein. The data presented here indicate the presence of time-dependent immune responses in EAE-bearing mice, which may be associated with the Th1 and Th17 subpopulations of T-cells. Thymulin and thymopentin demonstrated different patterns of activity, most likely via mechanisms involved in NF-kappa B signalling and Hsp72 expression.

Topics: Animals; Cells, Cultured; Cytokines; Disease Models, Animal; Encephalomyelitis, Autoimmune, Experimental; HSP72 Heat-Shock Proteins; Humans; Male; Mice; Mice, Inbred Strains; Multiple Sclerosis; Myelin Basic Protein; NF-kappa B; Th1 Cells; Th17 Cells; Thymic Factor, Circulating; Thymopoietins; Thymus Gland

The paper is concerned with interaction of the immune, endocrine and nervous systems in patients with multiple sclerosis. Dexamethasone and vasopressine tests were made. Lymphocyte sensitivity to hydrocortisone and thymalin, the main protein of myelin, was detected. It is advisable that arginine-vasopressine combined with thymalin be used for correction of homeostatic abnormalities and secondary disease prophylaxis.

Topics: Adrenal Cortex Function Tests; Adrenal Glands; Adrenocorticotropic Hormone; Adult; Female; Homeostasis; Humans; Hydrocortisone; Immunoglobulins; Male; Middle Aged; Multiple Sclerosis; Pituitary Function Tests; Pituitary Gland, Anterior; Rosette Formation; T-Lymphocytes; Thymus Hormones

Topics: Adjuvants, Immunologic; Adult; Antibody Formation; Antigen-Antibody Complex; Drug Evaluation; Female; Humans; Immunity, Cellular; Male; Multiple Sclerosis; Peptides; Thymus Extracts; Thymus Hormones

Thymus-dependent immunity as well as thymic factor and corticosteroid influence upon it were studied in 36 patients with disseminated sclerosis. The illness was diagnosed according to the Poser system with the help of the spontaneous erythrocyte rosette test. The sensitivity of T lymphocytes to thymaline, to basic myelin protein and to prednisolone was analyzed. The Soviet drug thymaline, obtained from calf thymus, was first used for the treatment of disseminated sclerosis. Clinical and immunological results turned out positive. The possibility of differential immunomodulating therapy of disseminated sclerosis is shown.

Topics: Adjuvants, Immunologic; Adult; Humans; Immunologic Deficiency Syndromes; Leukocyte Count; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Prednisolone; Rosette Formation; T-Lymphocytes; Thymus Hormones

Topics: Animals; Cell Differentiation; Encephalomyelitis, Autoimmune, Experimental; Guinea Pigs; Male; Multiple Sclerosis; T-Lymphocytes; Thymic Factor, Circulating; Thymus Hormones