Morphological Characteristics of the Thymus and Spleen and the Subpopulation Composition of Lymphocytes in Peripheral Blood during Systemic Inflammatory Response in Male Rats with Different Resistance to Hypoxia.

Vladimir A Mkhitarov,Dmitry N Khochanskiy,Anna M Kosyreva,Olga V Makarova,Dzhuliia Sh Dzhalilova,Natalia A Zolotova,Ivan S Tsvetkov,Mikhail E Diatroptov

doi:10.1155/2019/7584685

Abstract

On the model of the systemic inflammatory response (SIRS), induced by lipopolysaccharide (LPS), the morphological and functional changes in the thymus and spleen and the subpopulation composition of peripheral blood lymphocytes of rats differing in resistance to hypoxia were studied. It was demonstrated that the level of endotoxin in blood serum after 3 hours of LPS administration in susceptible-to-hypoxia rats was 64 times higher than in the control group, while in tolerant-to-hypoxia animals it was only 8 times higher in 6 hours. After 24 hours of LPS injection, only in susceptible-to-hypoxia rats did the level of C-reactive protein in blood serum increase. There is a difference in the dynamics of morphological changes of lymphoid organs after LPS injection in tolerant- and susceptible-to-hypoxia animals. After 3 hours of LPS administration, the tolerant-to-hypoxia rats showed no changes in the thymus, spleen, and subpopulation composition of lymphocytes in peripheral blood. After 6 hours there was only a decrease in B-lymphocytes and increase in cytotoxic T-lymphocytes and NK cells. After 1 day of LPS injection, the tolerant-to-hypoxia rats had devastation in PALS of the spleen. After 3 hours of LPS injection the susceptible-to-hypoxia animals had reactive changes in the lymphoid organs: decrease of the thymus cortex, narrowing of the marginal zones of spleen lymphoid follicles, widening of their germinal centers, and a decrease in the absolute number of cytotoxic T-lymphocytes, NK cells, and B-lymphocytes. After 24 hours of LPS injection the tolerant-to-hypoxia animals had a greater absolute number of T-lymphocytes and NK cells in comparison with the susceptible rats. Thus, in animals with different resistance to hypoxia the LPS-induced SIRS is characterized by different dynamics of morphological and functional changes of the thymus and spleen. The obtained data will serve as a basis for the development of new individual approaches to the prevention and treatment of infectious and inflammatory diseases.

Highlights

Many patient-specific factors, in particular age, sex, ethnicity, etc., have an impact on the severity, mortality, and survival rates of infectious and inflammatory diseases, including sepsis [1,2,3]
According to Enzyme-Linked Immunosorbent Assay (ELISA), the serum level of endotoxin after 3 h of LPS injection in the susceptible-to-hypoxia animals increased compared with the control group and was 36 times higher than in the tolerant ones (p=0.03)
Susceptible-to-hypoxia rats had a multiple increase in endotoxin level in serum after 3 h of LPS administration, which, apparently, causes a more pronounced inflammatory response: previously we have shown that, after 3 and 6 hours of LPS injection at a dose of 1.5 mg/kg, the increase in Nf-κb expression in the liver accompanied by an increase in serum IL-1β concentration is observed only in susceptible-to-hypoxia rats, which indicates the development of more pronounced LPS-induced inflammation in the livers of these animals

Summary

Introduction

Many patient-specific factors, in particular age, sex, ethnicity, etc., have an impact on the severity, mortality, and survival rates of infectious and inflammatory diseases, including sepsis [1,2,3]. Organisms with various resistance to the lack of oxygen differ in many parameters of integrative systems, such as the central nervous system, the endocrine system, and metabolism (antioxidant activity, mitochondrial enzyme complex I activity, level of norepinephrine, prolactin, corticosterone, etc.) [4, 9], International Journal of Inflammation including the content of hypoxia-inducible factor (HIF-1α), which is induced by hypoxia [5, 10]. Animals with different resistance to hypoxia have various adaptive abilities and predisposition to the development of inflammatory diseases: in susceptible-to-hypoxia animals, the 8-isoprostane level, which is a marker of oxidative stress, increases after hypoxic exposure. It is associated with damage of cellular macromolecules and an increase in the level of TGF-β [11]

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