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Morphofunctional state of neutrophils and cytokine status in patients with ovarian cancer

Tatyana Vladimirovna Abakumova, Inna Ivanovna Antoneeva, Tatyana Petrovna Gening, Dinara Rishatovna Dolgova, Snezhanna Olegovna Gening.

Abstract
The purpose of the study was to evaluate the morphofunctional state of polymorphonuclear neutrophils and cytokine levels in the lysate of blood neutrophils of ovarian cancer patients. The absolute and the relative number of peripheral blood polymorphonuclear neutrophils in 120 primary ovarian cancer patients (III-IV clinical stage FIGO) and 80 healthy women were determined. The expression of CD11a, 11b, 15 and CD95 in polymorphonuclear neutrophils was assessed by fluorescent microscopy. Cytochemically the myeloperoxidase activity, the content of cationic proteins, the activity in the spontaneous NBT-test and phagocytic activity in polymorphonuclear neutrophils was determined. The amounts of cytokines TNF-α, IL-1β, 1Ra, 6, 18, and G-CSF in serum were measured by the enzyme immunoassay method. Rigidity and topology of native polymorphonuclear neutrophils were assessed by scanning probe microscopy. To detect the differences between the data obtained in the evaluation of ovarian cancer patients and healthy people, a non-parametric U-Mann-Whitney test was used. Reliable difference was considered at p ≤ 0.05. These studies found an increase of the total number of polymorphonuclear neutrophils in peripheral blood, while reducing their cytotoxicity parameters. We observed reduced myeloperoxidase activity and level of cationic proteins. Reducing in the levels of CD15 and CD95 expression on the background of increasing polymorphonuclear neutrophils activity in the spontaneous NBT-test may indicate a decrease in ability to complete phagocytosis. The dynamics of CD11a and CD11b expression in polymorphonuclear neutrophils was multidirectional, and the changes were not statistically significant. Polymorphonuclear neutrophils membrane stiffness decreased in stage IV ovarian cancer. We also observed the levels of IL-1β reduced up to 248.5 9.00 pg / ml in stage III ovarian cancer, up to 230.9 15.04 pg / ml in stage IV ovarian cancer vs 36.8 10.74 pg / ml in control, reduced levels of 1Ra, and IL-18. We found that the level of IL-6 increased at stage III ovarian cancer up to 34.38 9.74 pg / ml vs 7.66 2.28 pg / ml in control, and the levels of TNF-α and G-CSF decreased. Thus, these results suggest a state of secondary immunodeficiency in patients with ovarian cancer at III-IV clinical stages of the disease.

Key words: ovarian cancer, cytokines, polymorphonuclear neutrophils, immunodeficiency



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