Search

The cell composition of leukocyte infiltrates in the endometrium, myometrium, and vaginal walls was studied in Wistar rats with modeled chronic endomyometritis after administration of IFNγ (0.1 μg/100 g body weight) in different daily regimens (10.00 or 20.00). Morning injections of this cytokine ameliorated inflammatory infiltration of the uterine wall and vagina, but increased the content of neutrophils in the endometrium. Evening cytokine injections reduced neutrophilic infiltration, enhanced mononuclear infiltration, and had no effect on plasmacytic infiltration of the uterine and vaginal walls. In the vaginal wall, both IFNγ administration schedules decreased neutrophil content. The data indicate the necessity to take into account the circadian rhythms in IFN therapy.

We studied the response of the pineal gland and organs of the immune system to melatonin treatment in Wistar rats kept under conditions of abnormal illumination regimen. The animals were kept under natural light regimen or continuous illumination for 14 days and then received daily injections of melatonin (once a day in the evening) for 7 days. Administration of melatonin to rats kept at natural light cycle was followed by a decrease in percent ratio of CD4+8+ splenocytes and CD4-8+ thymocytes. In 24-h light with the following melatonin injections were accompanied by an increase in percent rate and absolute amount of CD4+8+ cells in the spleen, and a decrease in percent rate of CD11b/c and CD4-8+ splenocytes. In the thymus amount of CD4-8+ cells increased, and absolute number of CD4+25+ cells reduced. Melatonin significantly decreased lipofuscin concentration in the pineal gland during continuous light. Direction and intensity of effects of melatonin on parameters of cell immunity and state of the pineal gland were different under normal and continuous light conditions. It should be taken into account during using of this hormone for correction of immune and endocrine impairments developing during change in light/dark rhythm.

We compared the effectiveness of immunomodulators used in the treatment of patients with chronic salpingitis and oophoritis with or without changes in succinate dehydrogenase (SDH) activity in blood lymphocytes at incubation with the drug. Diurnal variations in individual reaction of SDH in blood lymphocytes to thymalin or ridostin were revealed. In the groups of women receiving ridostin or thymalin during the reaction of lymphocyte SDH to it, improvement of clinical laboratory and immunological parameters was observed in the majority of the patients and no effect was found in a lesser group of patients than in the groups treated with drugs during the absence of lymphocyte SDH reaction thereto. The timing of the presence of SDH reaction to drugs in the immunocompetent cells makes it possible to set the optimal daily regime of their application and to select a drug that would be most effective in each particular case.

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.

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.

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.

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.

We demonstrate changes in cellular and humoral immunity in animals with experimental hyperthyroidism induced by chronic administration of potassium iodide (KI) solution. KI increased the weight and cellularity of the thymus and spleen and number of antibody-forming cells to sheep red blood cells and modified the relative content of T cell subpopulations. Phytosorption complex LimfoFit modifying cellular and humoral immunity affected only its individual parameters in hyperthyroid animals.

Changes in the cellular and humoral immunity parameters were revealed in animals receiving thyroxin and mercazolyl per os for 2 weeks. Specific features of effects of the hormone and its inhibitor on the parameters of immune system were found.

We analyzed activities of lysosomal cystein cathepsins B and L in mouse LS lymphosarcoma and its drug-resistant RLS 40 strain and their correlations with the dynamics of the percentage of cells with fragmented DNA and CD14 (+) phagocytes over 3 days after cyclophosphamide injection. LS regression and inhibition of RLS 40 growth after cyclophosphamide injection were paralleled by an increase in cathepsins B and L activities in tumor tissues. The antitumor effect of cyclophosphamide associated with apoptosis intensity and protease activities were significantly higher in LS. Positive correlations between activities of cathepsins B and L and the LS tissue content of cells with fragmented DNA and CD14 (+) phagocytes and negative correlations thereof with tumor weight were detected. It seems that the increase in cathepsins B and L activities in LS tissues was caused by cyclophosphamide induction of apoptosis and depended on the level of tumor cell infiltration with mononuclear phagocytes.

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 (+) 25 (high) thymocytes, and decreased the number of CD4 (+) 27 (low) splenocytes. These findings can serve as a prerequisite for the development of chronotherapeutic schemes for immunocorrection.

We studied the possibility of using anabolic steroid retabolil injections for complex correction of behavioral and immune parameters in rats with genetic predisposition to catalepsy. Subpopulation composition of lymphoid organ and blood cells was compared in rats with genetic predisposition to catalepsy and Wistar rats after retabolil administration. In rats predisposed to catalepsy, retabolil reduced the total content of thymus cells and increased absolute count of CD8 (+) thymocytes. In Wistar rats, retabolil increased the total cell count and the content of CD4 (+) thymocytes, but reduced the number of CD8 (+) cells. Therefore, changes in the subpopulation composition of thymus cells after retabolil administration were opposite in rats with genetic predisposition to catalepsy and Wistar rats. Retabolil injections reduced the severity of catalepsy response in rats with genetic predisposition. However, the time of freezing in Wistar rats significantly increased under these conditions.

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.

We studied the influence of abnormal illumination regimen on cell composition of the central and peripheral organs of the immune system in ISIAH rats and control WAG rats. In ISIAH rats, 24-h illumination for 14 days led to more pronounced inhibition of cell proliferation and differentiation in the thymus and more pronounced decrease in splenocyte proliferation and T and B cell counts in the spleen in comparison with WAG rats; however, the level of antigen-presenting cells in the spleen of ISIAH increased. We concluded that ISIAH rats are more sensitive to abnormal illumination regimen than WAG rats. Twenty-four-hour illumination was associated with impairments of central differentiation of T cells and activation of systemic inflammation followed by impairment of differentiation regulation, which can aggravate metabolic dysfunctions in these animals.

The effects of LPS from E. coli on DNA-binding activities of PPARα and PPARγ in the liver and immune system parameters of were studied in hypertensive ISIAH rats and normotensive WAG rats. In ISIAH rats characterized by low basal level of PPARα, PPARγ, and HDL, the response of the peripheral immune system compartment to LPS was more pronounced and was not associated with decrease in DNA-binding activities of PPARα observed in WAG. Proinflammatory stimulus did not induce proliferative changes in the thymus of ISIAH rats, which can reflect impaired relationships between the central and peripheral organs of the immune system. The character of regulatory interactions between PPARα and immune cells can differ in various rat strains and depend on initial PPARα activity, HDL level, specific features of immune status, resistance to stress, and hormonal and metabolic background.

The effects of chronic social defeat stress on the percentage of cells in different phases of the cell cycle and in apoptosis in the thymus and spleen of male mice were studied by the method of flow cytofluorometry. In stressed males, thymus weight decreased, the percent of proliferating thymocytes was significantly lower, and the percentage of G0-G1 cells was higher than in intact males. Stress substantially reduced the percentage of splenocytes in the G0-G1 phase and apoptotic cells, but the percentage of S and G2-M cells and proliferation index significantly increased. Chronic administration of anxiolytic diazepam prevented the majority of the changes in the percentage of cells in different phases of the cell cycle, but apoptosis in the thymus increased under these conditions. Possible association between cell cycle disorders, impairment of cell immunity, and chronic anxiety developing under conditions of long-term social defeat stress is considered.

We studied the effects of benzo(a)pyrene on lymphocyte chromatin in mice with experimental desynchronosis. Desynchronosis altered chromatin structure in immune system cells and suppressed the immune response. In mice with experimental desynchronosis, benzo(a)pyrene produced more pronounced changes in the chromatin structure compared to the control. It was inferred that light-dark cycle disturbances impair the resistance of organs and systems to damaging environmental factors.

Intestinal epithelium is a rapidly proliferating tissue and represents a unique model for the study of somatic stem cells. Here we summarized the data about markers, main properties, and methods of isolation of intestinal epithelial cells. Some aspects of molecular biology of the intestine are also discussed.

The production of cytokines by immunocompetent cells of intact mice was studied in various phases of the diurnal cycle. The ratio of produced cytokines was shown to differ in various phases of the diurnal cycle. The correlation between spontaneous production of various cytokines disappeared at 20:00, which reflects the development of physiological immunosuppression due to evening increase in physical activity of mice and corresponding changes in neuroendocrine status. Our results illustrate the existence of diurnal variations in intercellular interactions in the immune system. These data should be taken into account in the study of the mechanisms for cytokine immunoregulation and development of new schemes for cytokine immunocorrection.

We studied hemopoiesis- and immunopoiesis-restoring activity of small intestinal epitheliocytes in lethally irradiated mice. The populations of peripheral blood cells and parameters of humoral and cellular immune response in lethally irradiated mice returned to normal 6 months after transplantation of cells from the small intestinal epithelial layer. Study of the distribution of intestinal cells in the body after transplantation showed long-term persistence of the donor cells in tissues of lethally irradiated animals. These data attest to high hemopoietic potential of small intestinal cells.

Circadian variations in the immune status and serum melatonin were studied in asthmatics during exacerbation stage before and after treatment. Deviations from the normal (donor) immunogram values at 9.00 and 21.00 and decreased correlations between immune values and blood melatonin level were detected. The correlations of immune values between each other and with melatonin over the circadian cycle increased after treatment.

Circadian variations in spontaneous and concanavalin A-stimulated proliferation of mouse thymocytes and splenocytes were studied after administration of recombinant interleukin-2 at different times of day. Differences were revealed in the effect of morning and evening treatment with the cytokine. The time of injection corresponded to various phases of the natural circadian rhythm of endogenous interleukin-2 production, which probably contributes to diurnal differences in the influence of this cytokine.

The effect of melatonin on disturbed circadian variations in the lymphocyte subpopulation composition of the thymus and inguinal lymph nodes was studied in CBA mice exposed to constant illumination for 14 days. The desynchronizing effect of permanent illumination on the thymus consisted in disappearance of circadian variations in the total number of thymocytes, absolute count of thymocytes, absolute counts of CD8(+) and CD4(+) cells, and in inversion of changes in the absolute counts of CD4(+)8(+) cells from 15.00 to 20.00. In lymph nodes circadian variations in the percentage of CD4(+)+ lymphocytes disappeared, while absolute counts of CD4(+)8(+) and CD8(+) cells changed from 15.00 to 20.00. Melatonin restored circadian dynamics of some parameters mainly in the thymus.

We studied the effect of benzo[a]pyrene on cells of lymphoid organs, energy metabolism of blood lymphocytes, and immunological reactivity in mice with anxious depressive syndrome produced by social stress. Benzo[a]pyrene exhibited a more pronounced immunotoxic activity in anxious-depressive animals, which was more than a simple sum of the effects produced by adverse ecological and psychic factors.

Experiments on (CBA x 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.

Parameters of the immune status of the thymus and spleen in rats with genetic catalepsy were lower compared to those in Wistar rats. Diurnal variations in cell subpopulations of lymphoid organs were different in animals of these strains. Behavioral characteristics and neuroendocrine state in rats with genetic catalepsy were associated with specific changes in the immune system and neuroimmune interactions.

The population of epithelial cells in the small intestine includes precursor cells of hemopoiesis possessing the ability to form splenic colonies on day 8. Intestinal epithelial cells stimulates proliferative and colony-forming activity of hemopoietic stem cells by producing granulocyte-macrophage colony-stimulating factor.

Salivary content of melatonin and parameters of the immune status were studied in young healthy individuals. Morning and evening levels of melatonin showed different correlations with some immunity parameters. It was assumed that the degree and type of correlation between the immune system and melatonin depend on the phase of circadian cycle, which should be considered during evaluation of immunoendocrine status.

Examination of populations living in regions of fallout radiation revealed changes in the distribution of HLA genes not only in irradiated individuals, but also in their children and grandchildren. Combined irradiation of inbred mice in comparable doses showed that H-2 genes determine immune reactions in animals and their offspring to radiation. Our results indicate that the immune system in mammals is immunogenetically regulated by low-dose radiation.

Protective properties of a new enterosorbent noolith (lithium ions immobilized on mineral matrix) were studied in C57Bl/6J mice predisposed to depression caused by intermale confrontations. The drug was administered daily for 15 days after the 5th confrontation and then the animals were tested in the forced swimming test. The number of specific(3)H-8-OH-DPAT binding sites in 3 brain regions was determined. It is shown that noolith produced an antidepressive effect manifested in decreased immobility time in the Porsolt test. Moreover, noolith reduced the number of 1A-serotonin receptors in the frontal cortex and hypothalamus. It is concluded that noolith possesses protective properties.

We studied the effects of amitriptyline on diurnal variations of oxidative-reduction enzyme activities (succinate dehydrogenase, lactate dehydrogenase, and NADPH diaphorase) in rat peripheral blood lymphocytes during experimental desynchronosis. Desynchronosis was induced by constant light exposure for 14 days and manifested in a morning shift of maximum lactate dehydrogenase activity and elevated morning NADPH diaphorase activity. Amitriptyline normalized morning lactate dehydrogenase activity and diurnal variations in NADPH diaphorase activity.

Levels of the major regulatory subpopulations of lymphocytes in the thymus and spleen and blood lymphocyte dehydrogenase levels were measured in male mice with aggressive and submissive patterns of behavior formed over 10 or 20 aggressive confrontations leading to repeated experience of victory or defeat. The results showed that repeated experience of social confrontation non-specifically increased the proportion of segmented neutrophils and lactate dehydrogenase activity in both participants in aggressive encounters, and decreased the numbers of CD4+ and CD8+ T-lymphocytes in the spleen. Succinate dehydrogenase specifically decreased in the lymphocytes of aggressive mice and increased in the lymphocytes of submissive mice. The proportion of CD4+ T-lymphocytes in victims' thymuses also decreased. Changes in metabolic measures and percentage ratios of lymphocyte contents were dynamic and depended on the duration of confrontational interactions.

We studied the effects of amitriptyline (preparation stimulating melatonin synthesis in the pineal gland) on daily variations of cell composition in immune organs of Wistar rats with experimental desynchronosis. Amitriptyline administered in the evening restored the daily dynamics of the number of thymus cells.

Plasma content of thymosin-alpha(1)and its circadian variations in patients with inflammatory gynecologic diseases differ from those in healthy donors and depend on the type of inflammation and efficacy of treatment. It is concluded that not only the absolute content of thymic hormones, but also their biorhythmic variations are important for immune regulation.