Вміст гемопоетичних стовбурових клітин у крові та особливості імунного статусу людей з різною стійкістю до гіпоксії

Abstract

Intermittent hypoxia treatment (IHT) is gaining attention as a clinical modality due to its capacity to protect cells, tissues, organs, and the whole organism from more intense and/or sustained hypoxia, ischemia and other stresses, to enhance physical and mental capacity. Circulating hematopoietic stem and progenitor cells (HSPC) play an important role in immune response to hypoxia ensuring tissue reparation processes, formation of all types of blood cells etc. There exist considerable individual differences in the capability to mobilize HSPC. This study was designed to compare the effects of IHT on HSPC, various factors of natural resistance and main humoral and cellular components of adaptive immunity in peripheral blood of subjects with normal and reduced tolerance to hypoxic load. Ten healthy male volunteers (age 30,9 +/- 0,6 y.o.) participated in the study and were divided into two groups with reduced (RT, 5 subjects) and normal (NT, 5 subjects) hypoxic tolerance. Criterion for reduced hypoxic tolerance detection was the exceeding deviation of arterial blood pressure, minute ventilation, SaO2 and/or pathological changes in ECG during sustained hypoxia test (breathing with 10% oxygen, 10 min). All subjects were studied before and after a 14 day IHT program consisting of four 5 min bouts/d of breathing 10% O2, with intervening 5 min room air exposures. Immunofluorescence detected HSPCs as CD45+CD34+ cells in peripheral blood. Phagocytic and bactericidal activities of neutrophils, circulating immunoglobulins (IgM, IgG, IgA), immune complexes, complement, and cytokines (EPO, TNF-alpha, IL-4, IFN-gamma) were measured. It was shown that NT subjects had higher hemoglobin and erythrocytes level, hematocrit and physical working capacity, but leukocytes, lymphocytes, CD8+-cells contents and level of IgA were lower than in RT. These differences were preserved after IHT course. CD45+34+cells content was the same in both groups before IHT, but RT subjects demonstrated twice decrease in HSPCs content after IHT as opposed to NT who did not show distinct reactions. A decrease in HSPCs is probably associated with the change of their migration capacity. However, it remains unclear whether there is an inhibition of HSPCs migration into circulation or an activation ofHSPCs escape from circulation. In both cases tissues could accumulate more HSPCs which in turn could enhance hematopoiesis and general regenerative potential. RT group also had lower complement, induced and reserve bactericidal activities of neutrophils which were significantly increased after IHT reaching the level of NT. The level of cytokines EPO, TNF-alpha and IFN-gamma did not differ in both groups before IHT but considerably reduced level of IL-4 was registered in RN patients. IHT sharply lowered pro-inflammatory cytokine TNF-alpha in both groups, significantly increased IL-4 in RT subjects; increasing behavior of IFN-gamma was observed in both groups. EPO was not affected considerably during the study. The findings support the potential for eventual application of IHT for immunotherapy, especially for patients with reduced hypoxic tolerance.