E. V. Mel’nikova

Blood Microvesicles during Chronic Lymphoproliferative Diseases

The levels of CD19+ and CD20+ microvesicles were estimated in the blood of patients with B-cell chronic lymphocytic leukemia and indolent non-Hodgkin lymphoma by flow cytometry method. It was found that the number of B cell microvesicles is several times higher in patients than in volunteers. The level of CD20+ microvesicles directly correlated with the number of CD20+ lymphocytes in patients with chronic lymphoproliferative diseases. Extramedullary tumors cells can be a source of CD19+ microvesicles.

Proliferative Activity and Subpopulation Pattern of Cells in Murine Thymus and Spleen on the Model of Graft-Versus-Host Chronic Reaction under Various Diurnal Regimens of IL-2 Administration

We studied the effects of IL-2 administration at different times of day to female B6D2F1 mice with experimental immunopathology, graft-versus-host chronic reaction induced by the administration of lymphoid cells from parental female DBA/2 mice. Recombinant murine IL-2 was injected subcutaneously at 10.00 (group 1) or 16.00 (group 2) after the first cell transfer. Evening administration of IL-2 in contrast to its morning injection prevented cell proliferation in the thymus and spleen, decreased the number of apoptotic splenocytes, significantly stimulated differentiation processes in the thymus, increased the amount of CD4+25high thymocytes, and decreased the number of CD4+27low splenocytes. These findings can serve as a prerequisite for the development of chronotherapeutic schemes for immunocorrection.

Chronodependent Effect of Interleukin-2 on Mouse Spleen Cells in the Model of Cyclophosphamide Immunosuppression

We studied the chronodependent effect of IL-2 in the experimental model of immunodeficiency, cyclophosphamide-induced immunosuppression in mice. IL-2 in a dose of 100 U/ mouse was administered at 10.00 and 16.00 for 3 days after injection of cyclophosphamide. In contrast to the morning treatment with the cytokine, evening administration produced antiapoptotic effect on splenocytes and stimulated proliferation to a greater extent. This was accompanied by an increase in the number of CD4+, CD25+ and CD4+25+ cells in the spleen to a level of intact mice. More pronounced effect of the evening mode of IL-2 administration on the proliferation and subpopulation composition of mouse spleen cells in the studied model can be associated with high blood level of CD25+ cells at this time of the day.

Bezafibrate causes depression of the immune response and increases the sensitivity to endotoxin in association with low level of HDL and PPARα activity in hypertensive ISIAH rats.

We studied the effect of bezafibrate on hepatic PPARα activity and immune parameters in hypertensive ISIAH rats in comparison with normotensive WAG rats under conditions of LPS treatment. Bezafibrate increased activity of PPARα in WAG rats, but not in ISIAH rats. As differentiated from WAG rats, bezafibrate produced a potent effect on the content of T cell subpopulations in the thymus and spleen of ISIAH rats. Administration of LPS after injection of bezafibrate caused death of 50% ISIAH animals (but not WAG rats), which was associated with low level of HDL cholesterol and increased triglyceride content. Our results suggest that the hypolipidemic treatment (e.g., bezafibrate) can increase the severity of complications in patients with infectious and inflammatory diseases in association with low level of HDL.

Effect of Experimental Desynchronosis on Immunotoxicity of Benz(a)pyrene in (CBA×C57Bl)F1 Mice

Experiments on (CBA×C57Bl)F1 mice showed that constant (day and night) illumination for 2 weeks led to the development of internal desynchronosis, which significantly modulated the reaction of the immune system to benz(a)pyrene compared to those in intact animals. Presumably, the differences were associated with changed circadian rhythms of the immune parameters in experimental animals determining different ratios and, presumably, functions of immunocompetent cells during benz(a)pyrene exposure in intact controls and animals with desynchronosis.

Changes in the Interaction of the Pineal Gland and Immune System Organs in Rats in Response to Administration of Melatonin in Conditions of an Altered Light Regime

The aim of the present work was to use correlation analysis to identify the complex reaction of the pineal gland (PG) and immunocompetent organs in response to administration of melatonin (MT) in conditions of an abnormal light regime. Animals were kept for 14 days with natural or round-the-clock illumination (RTCI). Animals then received 0.9% sodium chloride solution or MT for seven days, after which they were decapitated and measurements were made of body, PG, thymus, and spleen weight. Thymus and spleen lymphocyte subpopulations were assessed by flow cytometry. PG lipofuscin content was determined in terms of autofluorescence intensity on frozen sections at wavelengths over the range 560–600 nm. The number of intraorgan relationships within the immune system was found to increase in response to MT regardless of light regime. Administration of MT to animals subjected to RTCI decreased the number of interorgan relationships, with the appearance of negative correlations between PG lipofuscin content and the cellular composition of the spleen. The most marked synchronizing and adaptogenic effects of MT were seen in RTCI conditions.

Effects of Roncoleukin on Measures of Immunity and the Anxious-Depressive State Induced by Chronic Social Stress in Male Mice

Chronic social stress leads to the development of an anxious-depressive state in male mice, accompanied by impairments to cellular and humoral immunity. The aim of the present work was to study the influences of the immunostimulator Roncoleukin on different components of immunity and psychoemotional status in depressed male mice. Roncoleukin (5000 IU/kg, i.p.) and reference agent physiological saline were given to anxious-depressed male mice for two weeks on the background of relative tranquility. At this point, the cellular compositions of the thymus, spleen, and blood were studied. The effects of Roncoleukin on communicativeness, anxiety, and depressivity, as assessed in behavioral tests, were also investigated. Roncoleukin decreased thymocyte and splenocyte counts, though there was an increase in the number of blood leukocytes and an increase in the mass index of the thymus. Roncoleukin increased the proportion of CD4+8+ lymphocytes in the thymus, and also increased the proportions of CD8+ and CD3+25– cells in the spleen. Anxiogenic, stimulatory, and mild antidepressant effects were seen. Roncoleukin had little effect when used in the complex treatment of impaired immunity and psychoemotional disorders evoked by chronic social stress.

Effect of Diprotin A, an Inhibitor of Dipeptidyl Peptidase IV, on Immunological Parameters of Lymphocytes in Intact Animals and Animals with Experimental Autoimmune Process

We found the peculiarities of the effects of dipeptidyl peptidase IV inhibitor diprotin A on immunological parameters of lymphocytes in lymphoid organs in intact animals and in animals with experimental autoimmune process. In intact animals, diprotin A increased cellularity of the thymus and spleen, number of CD4+, CD8+, and CD4+8+ thymocytes and CD3+ splenocytes and reduced cellularity of lymph nodes and the number of antibody-forming cells in the spleen. Diprotin A administered against the background of autoimmune process, reduced thymus cellularity, number of antibody-forming cells in the spleen, and number of CD4 and CD4+8+ thymocytes in comparison with the corresponding parameters of autoimmune process.

Effect of Melatonin on Cellular Composition of the Spleen and Parameters of Lipid Metabolism in Rats with Alimentary Obesity

We studied the effects of melatonin on the status of immune organs and parameters of lipid metabolism in rats with alimentary obesity and parameters of lipid metabolism and immune status in Wistar rats kept on high-fat diet and receiving melatonin solution per os. Melatonin leveled the changes in blood and liver parameters of lipid metabolism, which was paralleled by normalization of cellular composition of immune organs. We conclude that melatonin can be a promising agent for the treatment of lipid metabolism and immune status disorders in alimentary obesity.

Effects of Dipeptidyl Peptidase IV Inhibitor Sitagliptin on Immunological Parameters of Lymphocytes in Intact Animals and Animals with Experimental Autoimmune Process

The effects of dipeptidyl peptidase IV inhibitor sitagliptin on immunological parameters were studied in animals with experimental autoimmune process. The effects of the drug administered in preventive (before manifestation of autoimmune processes) and therapeutic (after manifestation of autoimmune process) modes were studied.