Besides the well-known effects upon bone metabolism, vitamin D (VD) plays important roles in many other processes in the body, including immune regulation. VD action is carried out through its cellular membrane receptor, which is expressed in a variety of human organs and tissues, e.g., most cells of immune system, as well as epithelial cells lining the mucous membranes. The cell-membrane bound VD receptor is transferred to the cytoplasm, to form a functional complex with vitamin A and its receptor. This complex provides either inhibiting, or enhancing effect upon transcription of hundreds genes in the nuclear DNA, including those that regulate cell growth, differentiation, apoptosis, thus preventing malignancy and angiogenesis. The following effects of VD are supposed with respect to immune system: VD inhibits antigen presentation by dendritic cells, supresses Th1-cell differentiation and the production of Th1-cytokines, shifts the balance of Th1/Th2 cell responses towards the Th2 response, exerts inhibitory effect upon Th17 cells, promotes Treg cell development, and increases their activity. In addition, VD boosts production of «endogenous antibiotics» that may provide powerful effects upon Gram-positive and Gram-negative bacteria, fungi and viruses. Therefore, VD seems quite important for prevention of autoimmune and atopic diseases: multiple sclerosis, rheumatoid arthritis, type 1 diabetes, Crohn’s disease, ulcerative colitis, development of asthma in children and chronic obstructive pulmonary disease. VD protects from a wide range of infections, including tuberculosis, leprosy and respiratory infections, and prevents the development of several tumors. Almost half the population of different countries has a VD hypovitaminosis, often hidden and undiagnosed, and this can be a leading cause of weakened immunity and increased morbidity. The diagnostics of VD hypovitaminosis, prevention and treatment of hypovitaminosis should be among the most important healthcare tasks in Russia.

This study presents data upon the effects of CpG oligonucleotide substance (CpG ODN 2006). The commercial preparation was applied in vitro as a single agent, or in combination with various cytokine production inducers. Spontaneous and induced cytokine levels were tested in cultures of human blood cells taken from the persons before and after anti-plague vaccination. It has been shown that the vaccination had no effect upon spontaneous production of cytokines participating in innate (IL-8, TNFα) and adaptive (IFNγ, IL-4) immunity. CpG ODN 2006 proved to exert effects upon functional activity of human blood Th1 and Th2 pro-inflammatory cytokines after the first vaccination with live anti-plague vaccine, being reflected as higher Th1/ proinflammatory (IL-17 and IFNг) and Th2/ antiinflammatory (IL-4) cytokine production. Postvaccination changes of IgM, IgG, IgA, and IgE contents were non-significant. Following repeated vaccination, the CpG ODN 2006 induced an increase of IL-4 and IL-17 production in blood cells, as well as decrease in IFNг levels. Thus, the ability of CpG ODN 2006 to activate the cells participating in innate and adaptive immunity opens some prospects for usage of this oligodeoxynucleotide in the development of more efficient anti-plague vaccines.

We have analyzed clinical and laboratory data for 256 women surveyed in early pregnancy, being later classified by their pregnancy outcomes, i.e., placental insufficiency (n=106), interruption in the first trimester (n = 38) and uncomplicated cases with delivery of live, full-term infants (n = 112). We evaluated serum levels of cytokines and their soluble receptors, as well as spontaneous and induced cytokine production by whole blood cells and intracellular synthesis of IFNг and IL-4 by the T-helpers from peripheral blood. It was shown that the cases complicated with subsequent compensated placental insufficiency are associated with activation of mitogen-induced cellular production of IL-1в, whereas development of subcompensated placental insufficiency is associated with increased serum levels of IL-1в and IL-1ra at early terms of gestation. An increased mitogen-induced synthesis of IFNг in blood cells represents a common risk factor for subcompensated placental insufficiency and miscarriage in the first trimester of gestation. Along with elevated mitogen-induced interferonogenesis, cellular overproduction of IL-2, as well as increased intracellular synthesis of IFNг and IL-4 by T-helpers under additional stimulation, accompanied by a growing polarization of Th1/Th2 are predictive for early reproductive losses. 

The aim of this study was to evaluate expression rates of phosphorylated STAT3 (рSTAT3) transcription factor in peripheral blood mononuclear cells (PBMC) and some features of its modulation by leptin in various clinical forma of bronchial asthma (BA). 

Materials and methods. We evaluated 25 healthy persons and 62 BA patients. pSTAT3 expression in PBMC was measured by means of flow cytometry.

Results. A phenomenon of increased pSTAT3 expression was registered in PBMC from BA patients. A most sufficient elevation of pSTAT3 levels was revealed in allergic clinical variant of the disorder. Leptin was shown to increase pSTAT3 expression in PBMCs from healthy persons only. In allergic BA, such effect of leptin was not observed, whereas a trend for pSTAT increase was shown in non-allergic BA. In allergic BA, we have revealed a direct correlation between the STAT3-mediated leptin signaling index and bronchial patency parameters. Appropriate inverse correlation was registered in non-allergic BA.

Conclusion. We have revealed some characteristics of рSTAT3 expression in PBMCs and its modulation by leptin in various clinical forms of BA, thus providing a potential basis for development of targeted therapy aimed for transduction of different cytokine signals mediated by STAT3 transcription factor.

This clinical trial included 63 patients with lung adenocarcinoma who underwent radical surgical resection of the tumor at the Thoracic Surgery Department of Rostov Research Oncological Institute from 2009 to 2011, The patients were randomized in two groups, i.e., 33 patients (52%) of the main group received adjuvant chemoimmunotherapy accomplished with Ingaron, whereas 30 cases (48%) in control group were assigned to receive conventional adjuvant chemotherapy. Adjuvant chemoimmunotherapy was administered according to the following schedule: carboplatinum, AUC = 5 i.v. on day 1; etoposide, 100 mg/m2 i.v. on days 1,3,5; interferon-gamma, 500.000 I.E./m2 i.v. on days 2,4,6. In the patiens undergoing lobectomy, carboplatinum was replaced for cisplatinum 100 mg/m2 i.v. on day 1. Comparative evaluation of the both treatment regimens has shown a correcting effect of Ingaron upon cellular immunity links. The Ingaroncontaining chemoimmunotherapy may contribute to improvement of 3-year event-free survival among lung adenocarcinoma patients by 19 percent (p = 0.06607).

The major medical problem in the treatment of skin melanoma is improvement methods of treatment, increasing their effectiveness and safety. In this study, adoptive immunotherapy, using lymphocytes activated in vitro, was performed in 15 patients with metastatic melanoma. Evaluated the phenotype of peripheral blood lymphocytes and activation markers (HLA-DR, CD25, CD314, CD38, CD69) before and 3-4 weeks after immunotherapy. It is shown that for these patients is characterized by increasing the number of CD25+ and Treg lymphocytes in the bloodstream, which has not changed after immunotherapy. Adoptive immunotherapy in combination with chemotherapy resulted in a decrease of absolute number of lymphocyte, B- and T-lymphocytes, T helper cells, NKT-cells, CD314+ lymphocytes, CD38+ lymphocytes and immature T-lymphocytes (CD3+CD38+) (р < 0,05). However, there was a positive dynamic to increase the percentage of NK-cells to 32% and CD69+NK-cells to 21% and significant increase in expression of HLA-DR on all lymphocytes (p < 0.05). Adoptive immunotherapy characterized by the absence of side effects and can be recommended as accompanying to basic radiation and chemotherapy.

We have previously shown that acute traumatic brain injury (TBI) is accompanied by increased level of circulating bone marrow progenitors, and favorable outcome is associated with early mobilization of CD34+CD45+ hematopoietic progenitor cells (HP). The present study was aimed at investigating whether patients with early HP mobilization differed from those with mobilization failure by systemic inflammatory reaction and immune parameters. The TBI patients were characterized by increased levels of serum C-reactive protein (CRP), IL-1в, IL-6, IL-8, MCP-1, G-CSF and IL-1ra indicative for presence of systemic inflammatory response. Importantly, patients with lacking mobilization of early HPs were shown to have significantly higher serum levels of CRP, MCP-1, MIP-1в, and G-CSF and a lower level of VEGF. In addition, patients with lack of early HP mobilization differed by significantly lower absolute number of lymphocytes, CD3+ T cells, CD4+ T cells, CD16+ NK cells and proliferative response of mononuclear cells to stimulation with ConA as well as by 4-fold higher rate of infectious complications compared with the opposite group. These data suggest that correlation of early mobilization of CD34+CD45+ cells with a favorable outcome in TBI patients may be partially mediated by anti-inflammatory and immunomodulatory effects of circulating bone marrow progenitors.

We have performed immunohistochemical staining of lymphocyte subpopulations (CD16+, CD56+, CD20+, CD138+), and HLA-DR antigen (II class) using monoclonal antibodies by “Novocastra” (United Kingdom). The cell were counted in uterine scrapings of patients with verified chronic endometritis (CE). The samples were taken before and after treatment. The endometritis treatment was carried out according to standard procedures. In a group of patients, rehabilitation treatment was made by means of CAPELM-01 “Andro-Gin”, whereas another group was treated by of hormone replacement therapy and combined physiotherapy with CAP-ELM-01 “Andro-Gin”. There was a significant reduction of cytotoxic lymphocytes after treatment applied.