PhD Scientific Days 2025

Poster Session III. - C: Molecular Medicine

Ex Vivo Cytokine Production by Blood Cells for Hypoxia Tolerance Determination

Name of the presenter

Dzhalilova Dzhuliia

Institute/workplace of the presenter

Petrovsky National Research Centre of Surgery

Authors

Dzhuliia Dzhalilova¹, Ivan Tsvetkov¹, Anna Kosyreva¹, Nickolay Fokichev^1,2

1: Petrovsky National Research Centre of Surgery
2: Faculty of Biology and Biotechnology, HSE University

Text of the abstract

Introduction. Hypoxia-tolerant and hypoxia-susceptible organisms exhibit distinct severity levels in local and systemic inflammatory and tumor processes. Current methods for hypoxia tolerance determination require direct exposure to oxygen deficiency, which limits their applicability. Therefore, identifying biomarkers capable of predicting individual hypoxia tolerance without subjecting the organism to hypoxic conditions remains a critical research objective.
Aims. The aim of the study was to assess whether ex vivo cytokine production by blood cells can serve as a predictive biomarker for hypoxia tolerance in Wistar rats.
Methods. In male Wistar rats, blood was obtained from the tail vein; to evaluate spontaneous cytokine production, blood cells were incubated for 24 hours in a CO2 incubator and the production of IL-6, IL-10, TNF-α was determined. To evaluate stimulated cytokine production, a complex mitogen consisting of E. coli lipopolysaccharide, phytohemagglutinin and concanavalin A in final concentrations of 2 μg, 4 μg and 4 μg, respectively, which stimulates cytokine production by leukocytes, was added to the blood. Stimulated blood cells were incubated for 24 hours in a CO2 incubator, then IL-1β production was determined. Fourteen days after blood sampling, rats were placed in a decompression chamber at 11,500 m altitude to determine their hypoxia tolerance using the generally accepted method. Rats with a "gasping time" (the time from the moment of rising to the "altitude" until the adoption of a lateral position) of more than 240 sec (n=7) were considered as hypoxia-tolerant group, and rats with a "gasping time" of less than 80 sec (n=11) were considered as hypoxia-susceptible group.
Results. Hypoxia-susceptible rats demonstrated significantly higher spontaneous production of both proinflammatory cytokines (IL-6, TNF-α) and anti-inflammatory IL-10 compared to tolerant animals. Following mitogen stimulation, only susceptible animals demonstrated increased IL-1β production. This enhanced cytokine responsiveness suggests a characteristic proinflammatory phenotype in hypoxia-susceptible animals.
Conclusion. The spontaneous and mitogen-stimulated production levels of IL-1β, IL-6, IL-10, and TNF-α demonstrate significant potential as biomarkers for assessing hypoxia tolerance.
Funding. The work was supported by the state assignment No. 123030700027-5.