PATHOGENETIC RATIONALE FOR IMMUNOMODULATORY THERAPY OF EXTERNAL GENITAL ENDOMETRIOSIS

The purpose of the investigation was to study the antiproliferative components of the immune system in patients with external genital endometriosis (EGE) and to develop pathogenetically warranted immunomodulatory therapy. The investigation was conducted at the D. O. Ott Research Institute of Obstetrics and Gynecology, North-Western Branch, Russian Academy of Medical Sciences (Saint Petersburg). The cytotoxic activity of natural killer (NK) cells and the parameters of the interferon (IFN) status in peripheral blood (PB) and peritoneal fluid (PF) were studied in relation to the extent of the disease. NK cell cytotoxicity index was determined by a cytotoxic test using as targets human erythromyeloid K-562 cells containing tritium-labeled uridine. The parameters of the IFN status in PB were estimated by a bioassay using as a test culture lung carcinoma L-41 cell lines susceptive to vesicular stomatitis virus. Induction of IFN-a/в by PB leukocytes was carried out by Newcastle disease virus; IFN-y production was induced by phytohemagglutinin or staphylococcal enterotoxin. The significant reduction was found in the cytotoxic activity of NK cells in PB and PF, which was negatively correlated with the extent of the disease (r=-0.46; p < 0.01). Analysis of the parameters of the IFN status in patients with EGE revealed higher total serum IFN levels than those in the control group; there was a significant decrease in the ability of PB leukocytes to produce IFN-a/в and IFN-y, which was most evident in grade IV EGE (the capacity for IFN-a/в production in EGE was 84.2±7.8 IU/ml; that in the control was 288.3+18.7 IU/ml; p < 0.001); the capacity for IFN-y secretion was 21.3+1.6 and 172.6+8.6 IU/ ml, respectively; p < 0.001). Immunomodulatory therapy is pathogenetically warranted by the obtained results. The use of an acridone IFN inductor was ascertained to cause a significant increase in NK cell cytotoxic activity and a rise in the ability of PB leukocytes to produce IFN-a/в and IFN-y. The stimulation coefficient that reflected an increment in the capacity of lymphoid cells for IFN production was highest in grades I and II genital endometriosis for IFN-a/в (256.2+21.7 and 89.2+6.8%, respectively) and in grades III and IV for IFN-y (47.6+4.2 and 396.5+33.2%, respectively).

endometriosis, interferon, natural killer cells, immunity, cycloferon