[Multiple sclerosis vaccine: possibilities of the use of dendritic cells immunomodulatory potential].

For the first time we carried out a clinical assessment of the safety, tolerability and clinical efficacy course of repeated administration of experimental modified autologous vaccine interleykin (IL-10) dendritic cells in two patients with secondary-progressive multiple sclerosis patient and one with relapsing-remitting multiple sclerosis. In the course of treatment, we carried out clinical and immunological monitoring. It was found out that intradermal dose of 3 x 106 cells applied to spinal area 6-12. times did not cause any serious side effects. After the treatment with dendritic cells, the following results were observed: 1) a significant positive clinical effect in patients with secondary-progressive multiple sclerosis exacerbations; 2) moderate positive clinical effect in patients with relapsing-remitting multiple sclerosis, in a state of remission; 3) a complete absence of any clinical results in patients with secondary-progressive multiple sclerosis without exacerbations. The immune response was characterized by a significant absolute and relative increase of serum T-regulatory cells. Discovered distinct anti-inflammatory properties of dendritic cell therapy allow us to consider it as a promising area of personalized treatment based on an individual vaccination against multiple sclerosis.

[Induction and protective properties of antibodies against muramyl peptides of gram-negative bacteria].

AIM: Characterize the role of humoral immune response in mechanisms of action of muramyl dipeptide immune stimulators. MATERIALS AND METHODS: Mice were immunized by a complex of muramyl peptides (CMP) obtained from Salmonella typhi peptidoglycan and consisting of 3 components: 1) N-acetyl-D-glucoasminyl-(beta1- > 4)-N-acetyl-D-muramoyl-L-alanyl-D-isoglutaminyl-meso-diaminopimelic acid (GMtri); 2) N-acetyl-D-glucosaminyl-(beta1- > 4)-N-acetyl-D-muramoyl-L-alanyl-D-isoglutaminyl-meso-diaminopimeloyl-D-alanine (GMtetra) and 3) GMtetra dimer (diGMtetra), in which monomeric residues of GMtetra are linked by an amid bond between carboxyl group of terminal D-alanine of one of GMtetra residues and omega-amino group of meso-diaminopimelic acid of the other GMtetra residue. RESULTS: Immunization resulted in a multifold increase of IgM, IgG1 and IgG2a titers against CMP. Antibodies were directed against the whole molecule of diGMtetra and did not recognize its fragments. Sera of mice immunized with CMP protected the mice from lethal infection with Gram-negative (S. typhimurium) but not Gram-positive (Staphylococcus aureus) microorganisms. CONCLUSION: Induction of protective antibodies may present a novel mechanism of action of muramyl dipeptide immune stimulators.

[The role of dopamine in the regulation of the interaction between nervous and immune systems in multiple sclerosis].

A complex neurological and neuropsychological examination, including the detection of depression, was conducted in 71 patients with multiple sclerosis aged from 23 to 62 years (mean age 43 ± 9 years). An immunobiochemical study included the analysis of expression of CD80 and CD86 on monocytes and B-cells, expression of TLR2 and TLR4 on monocytes, expression of D3 and D5 dopamine receptors on monocytes and B-cells, using flow cytometry, and the determination of Il-6, Il-10, IL-12p40 and dopamine plasma levels as well as vanillylmandelic acid (VMA, dopamine metabolite) urine levels measured with immunoenzyme assay. The results suggest the involvement of dopamine in the pathogenesis of depression in MS as assessed by dopamine and its metabolites levels. The role of dopamine and monocyte activation (by TLR2) in the pathogenesis of cognitive disturbances was specified as well.

[Significance of the functional activity of toll-like receptors and other receptors of the innate immune system of the kidney physiology].

The kidney needs to defend against microbial pathogens in order to maintain normal structure and function. This is achieved through innate and adaptive components of the immune system. For a long time, immunologists were concentrating on the adaptive immune system, which, as a result, was studied in detail; at the same time, the significance of the innate immune system was underestimated. This gap was partly filled in the recently, when the key role of the innate immune system in fighting microorganisms and in activating and regulating the adaptive immune system was convincingly established. In the first part of the present article, the sense apparatus of the innate immune system (the so-called pattern-recognition receptors) will be reviewed; particular attention will be paid to the toll-like receptors (TLRs), which bear the main burden of microorganism recognition. Signalling pathways that are activated by TLRs and result in the activation of effector mechanisms will also be reviewed. In the second part of the review, we will analyse available data on how these mechanisms of the innate immune system secure defence and normal functioning of the kidney.

Influence of cardiopulmonary bypass on the state of cognitive functions in patients with ischemic heart disease.

Forty patients with ischemic heart disease and undergoing aortocoronary shunting surgery with cardiopulmonary bypass were studied. All patients were subjected to neuropsychological assessment and immunochemical analysis of the production of chemokines (IL-8, IP-10, MCP-1, MCP-3, MIP-1 beta, SDF-1 alpha) and cytokines (TNF-alpha and IL-10). The aims of the study were to assess the presence and severity of cognitive deficit developing after surgery with cardiopulmonary bypass and to assess the effects of intraoperative Trasylol on its severity. Cognitive deficit on day 9 after coronary shunting with cardiopulmonary bypass was seen as impairments of attention, hearing-speech memory, visual memory, and dynamic praxis. Trasylol had a marked neuroprotective effect and suppressed the systemic inflammatory response. Patients given intraoperative Trasylol had no clinically significant cognitive deficit in the early post-operative period.

[Influence of cardiopulmonary bypass on cognitive functions in patients with ischemic heart disease].

Forty patients with ischemic heart disease subjected to coronary artery bypass graft surgery (CABGS) have been studied in conditions of cardiopulmonary bypass. All the patients underwent neuropsychological testing and enzyme immunoassay of chemokines (IL-8, IP-10, MCP-1, MCP-3, MIP-1, SDF-1alpha) and cytokines (TNF-alpha and IL-10). The study aimed at evaluation of the presence and severity of cognitive deficit developing after the surgery in conditions of cardiopulmonary bypass as well as of intrasurgery effect of tracilol on its expression. On day 9 after CABGS, there was an impairment of attention, audio-speech and memory and dynamic praxis. Tracilol exerted a pronounced neuroprotective action by inhibiting systemic inflammation response. Patients on intrasurgery treatment with tracilol did not demonstrate clinically significant cognitive deficit in the early postoperative period.

[Dendritic cells and their role in inflammation in the central nervous system]. / Dendritnye kletki i ikh rol' pri vospalenii v tsentral'noi nervnoi sisteme.

Dendritic cells play a key role in initiation and regulation of adaptive immunity against pathogens and tumors, as well as in autoimmune disease. In this article we review recent data regarding distribution of dendritic cells in the central nervous system, their role in responses and possible role in pathogenesis of multiple sclerosis. We also consider possibilities to use dendritic cells as immunotherapeutic targets in multiple sclerosis.