V. A. Trufakin

Circadian dynamics of cell composition of the thymus and lymph nodes in mice normally, under conditions of permanent illumination, and after melatonin injection.

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.

Circadian variations in immune values and serum melatonin in asthmatics

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.

Proliferative activity of cells in mouse thymus and spleen under different diurnal regimens of interleukin-2 administration.

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.

Effects of granulocyte-macrophage colony-stimulating factor produced by intestinal epithelial cells on functional activity of hemopoietic stem cells.

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.

Circadian variations in the metabolic reaction of human blood lymphocytes to hormonal stimuli in health and immunodeficiency

Circadian variations in the sensitivity of blood lymphocyte succinate dehydrogenase to thymalin and hydrocortisone are shown. The maximal sensitivity to thymalin is observed in the morning, and to hydrocortisone in the evening. The range of fluctuations in this parameter is wider in patients with immunodeficiency than in donors. Moreover, the direction of the lymphocyte metabolic reaction to the studied agents was found to be disturbed in the patients. The findings may be useful for designing chronotherapeutic schemes with the use of hormonal immunomodulating agents.

Effects of Melatonin on Morphological and Functional Parameters of the Pineal Gland and Organs of Immune System in Rats During Natural Light Cycle and Constant Illumination.

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.

Cell Cycle Arrest in the Thymus and Spleen in Male Mice under Conditions of Chronic Social Defeat Stress: Effects of Diazepam

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.

Structure of Nuclear Chromatin in Cells of Lymphoid Organs and Blood from Mice Maintained under Abnormal Light-Dark Cycle and Treated with Benz(a)pyrene

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.

Diurnal variations in lymphocyte subpopulations in lymphoid organs of rats with genetic catalepsy and Wistar rats.

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.

Effects of Amitriptyline on Diurnal Variations of Oxidation-Reduction Enzyme Activities in Rat Lymphocytes during Experimental Desynchronosis

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.