The role of cytotoxic cells and interferon system in regulation of processes of proliferation in endometriosis

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Introduction: Various components of immune system take part in pathogenesis of endometriosis. Their role might be paramount or minor during different periods of the disease. From our point of view, the most important is investigation of immune system in the aspect of immunological surveillance.

Objectives. To study changes of antiproliferative components of immune system in peripheral blood and peritoneal fluid in patients with endometriosis and to work out schemes of pathogenetic immune orientated therapy.

Materials and methods. 546 patients with endometriosis aged 20-44 were examined. The diagnosis was stated during surgery (493 laparoscopies and 53 laparotomies) and proved by the results of histology. The degree of dissemination was determined using R-AFS classification. 43 healthy fertile women were enrolled in control group. To specify the role of immune system in pathogenesis of endometriosis and as a method of control of effectiveness of immunomodulation therapy we prospectively evaluated interferon status and cytotoxic activity of NK-cells in peripheral blood and peritoneal fluid. The evaluation of NK-cells was carried out by radiometric test, in which cells of erythromyeloid line K-562 marked with Tritium were used as target cells. Interferon status was evaluated by biological test using lung carcinoma cells L-41 sensitive to the virus of vesicular stomatitis as a test culture.

Results. In patients with endometriosis we found a relative decrease of NK-cells’ activity in peripheral blood and peritoneal fluid in comparison with control group. Cytotoxic index (CI) of NK-cells had negative correlation with the degree of the disease (r = -46; p <0.01). CI of NK-cells in peritoneal fluid was equal to this index in peripheral blood. The relative increase of the level of total serum interferon in all patients with endometriosis in comparison with control group was revealed (p < 0.05). The level of total serum interferon in peritoneal fluid was relatively lower than its concentration in peripheral blood. When interferon status in patients with endometriosis was analyzed, we marked a relative decrease of lymphoid cells’ activity in secretion of α/β and γ-interferons which was maximal in patients with the IV degree of dissemination of endometriosis (ability to produce IFN-a/p was 66,3% lower; ability to secrete IFN-γ was 84,2% lower than in control group).

These alterations of immune system parameters enabled us to work out a pathogenetically proved scheme of immunomodulation therapy. After treatment with interferon inductor “Cycloferon” we found a rising of CI of NK-cells to normal values in all patients. The therapy led to the increase in ability of lymphoid cells to produce IFN-a/p in all groups of patients, except women with the IV degree of dissemination.

Conclusion. The decrease of NK-cells cytotoxic activity and lymphoid cells ability to produce а/p and γ-interferons indicate the alteration of immunological surveillance function in patients with endometriosis which plays a role in regulation of cell proliferation and implantation. When cytotoxic activity of NK-cells is lowered and ability of leucocytes in peripheral blood to produce α/β -interferons is preserved, it is expedient to use interferon inductors. When the potential ability of leucocytes to secrete a/p-interferons is absent, it is recommended to prescribe a course of interferon- replacement therapy (Reaferon, Viferon).

About the authors

М. I. Yarmolinskaya

Author for correspondence.
Email: info@eco-vector.com
Russian Federation, Saint-Petersburg

S. A. Selkov

Email: info@eco-vector.com
Russian Federation, Saint-Petersburg

References

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