The content of hypoxia-inducible factors and mediators of immunosuppression in the blood in diseases associated with hypoxia

The aim of the study was to identify general patterns and features of changes in the content of hypoxia-inducible factors-1 and -2 in association with an imbalance of cytokines (IL-10, IL-13, galectin-2 and -9, IFN-gamma) in the blood in diseases associated with hypoxia.

Materials and methods. We examined 25 patients with coronary heart disease (CHD) with heart failure II-III according to NYHA, 16 patients with chronic obstructive pulmonary disease (COPD) without exacerbation, 16 patients with infiltrative pulmonary tuberculosis (TB) before anti-TB therapy, and 18 relatively healthy donors. Plasma concentrations of HIF-1alpha, HIF-2alpha, IL-10, IL-13, galectins-2 and -9, and IFN-gamma were determined by enzyme-linked immunosorbent assay (ELISA).

Results. Positive outcomes of quantity determination of HIF-2alpha in the blood (24.00 ± 8.54 %, 75.00 ± 10.83%, 43.75 ± 12.40% of patients, respectively, against «zero» values in healthy donors) and also signs of immunosuppression at normal plasma concentrations of HIF-1alpha were determined in diseases associated  with chronic hypoxia (in patients with CHD, COPD, TB). Immunological insufficiency in CHD and TB is caused by a deficiency of IFN-gamma and galectin-2 in association with an excess of galectin-9 (in patients with CHD 1.10 [0.52; 2.60] pg/ml p = 0.038) or IL-13 (in patients with TB 0.81 [0.79; 1.40] pg/ml, p = 0.043), and in patients with COPD it is caused by a surplus of galectin-9 and IL-13 (8.50 [3.96; 15.00] pg/ml, p = 0.001 and 2.62 [1.20; 7.58] pg/ml, p = 0.002, respectively) at normal concentrations of IFN-gamma and galectin-2. The content of IL-10 in the blood tends to increase in CHD and COPD.

Conclusion. In patients with CHD, COPD and TB, chronic hypoxia is associated with immunosuppression mediated by an imbalance of IL-10, IL-13, IFN-gamma, galectins (2 and 9) in the blood and the secretion of HIF-2alpha, which has the property to stimulate the differentiation of M2-macrophages synthesizing anti-inflammatory cytokines.

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