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The high percentage of withdrawal of treatment due to the lack of clinical effect and intolerance to the drugs was identified during the treatment. Positive effect with respect to stabilization of MS course was found only in patients who earlier did not receive disease-modifying drugs. Double-blind studies are needed to resolve the question of the adequacy of brand-name drugs and generics.

Prolonged clinico-immunological observation of 85 patients with definite multiple sclerosis (MS) was performed in order to elucidate the connections between the clinical and immune state. A battery of immunological investigations was performed, including estimation of T-cell subpopulations in blood and cerebrospinal fluid (CSF); proliferative responses of circulating lymphocytes to mitogens, recombinant interleukin-2 (rIL2) and myelin basic protein levels in different culture conditions; levels of immunoglobulin (Ig) in sera and CSF, and of Ig production in vitro; indices of IL2 synthesis and IL2 sensitivity; production of prostaglandin E2 and tumour necrosis factor (TNF) alpha by monocytes and levels of beta-endorphin in sera and supernatants phytohaemagglutinin of (PHA)-activated cells. Clinical observation was performed periodically using Kurtzke scales and was supplemented by repeated recording of evoked potentials and magnetic resonance imaging. Initial investigations showed specific differences between patients with MS and the control groups (donors and patients with other neurological disorders of the same age). Correlative and regressive analyses showed no association between immunological and clinical parameters at the initial investigation, although immunological indexes were inter-related, and indicated specific alterations in immunoregulation in MS. Retrospective analysis revealed associations between the clinical status of patients with MS and their previous immune status. Evidence of cell activation--including a decreased percentage of circulating cells with differential antigens, lower cell mitogen-induced proliferative responses in vitro, with restoration following the addition of autoserum, greater IL2 sensitivity, and increased TNF-alpha production by macrophages--often predicted the clinical manifestation of deterioration. It is proposed that the immunopathological process in MS has a number of stages with characteristic features, and that progression from one stage to another can be subclinical. No single immunological index can be used to determine stage. Only systemic alterations reflect the real situation, whilst every patient has some abnormalities. A system of clinico-immunological monitoring could severe as the basis for a new approach to the dynamic treatment of MS.

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The surface phenotype of peripheral blood lymphocytes was studied in patients with different stages of multiple sclerosis and in healthy donors. There was no differences in the CD3 +, CD5 +, and CD8 + lymphocyte counts, while the count of CD4 + lymphocytes was slightly higher in patients with clinically active disease, i.e., with pronounced neurological symptoms. At the same time, the CD25 + lymphocyte count was considerably higher predominantly in patients with severe multiple sclerosis. It is suggested that the count of CD25 + lymphocytes can be used to determine the stage of multiple sclerosis.

For treating active forms of secondarily-progressing multiple sclerosis a preliminary clinical trial was performed by two courses: antibody-to-cytokine course (INT, INT and TNF) and cyclosporin А-course (sandimmun). Data of preliminary test of antibodies to cytokines evidence to possibility of performing further clinical trials "antibodies to INT and to TNF (to a lesser degree)" during active forms of progressive MS. Were obtained the results, evidencing to a possible use of sandimmun in constantly progressive forms of secondarily progressing disease, when favourable clinical effect coincided with supression of cytokine IL-2 production and lowering of activeness of immunocytes.

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