NATURAL-KILLER ACTIVITY IN STAGE-III AND STAGE-IV ENDOMETRIOSIS - IMPAIRED CYTOTOXICITY AND RETAINED LYMPHOKINE RESPONSIVENESS OF NATURAL-KILLER-CELLS

Our objective was to investigate the role of estrogens in the developm ent and progression of endometriosis, and evaluate the in vitro boosti ng effect of lymphokines on the activity of natural killer cells from endometriosis patients, with respect to the estradiol concentrations. Natural killer activity of peripheral blood was evaluated in 42 endome triosis patients who underwent laparoscopy for pelvic pain, infertilit y and benign adnexal masses, and it was correlated with serum estradio l levels. Twenty-five women with moderate and severe disease were re-e valuated for immune and endocrine parameters 4-8 weeks after surgery, before any specific adjuvant medical treatment, and analyzed for in vi tro responsiveness of cytotoxic cells to interferon (IFN) alpha 2 beta and interleukin-2 (IL-2) incubation. Patients with moderate and sever e endometriosis showed a significant decrease of natural cytotoxicity when compared with patients with mild and minimal disease (p = 0.01). The decrease of immune reactivity was independent of a reduced represe ntation of natural Killer cells, and persisted after surgical removal of all macroscopic endometriosis foci. A significant inverse relations hip was observed between natural killer activity and serum estradiol l evels, which resulted in moderate and severe disease (r = -0.4, p = 0. 009) but not in stages I and II. The in vitro responsiveness of cytoto xic cells to lymphokine incubation was preserved; both IFN alpha 2 bet a and IL-2 were able to increase the cytotoxicity of natural Killer ce lls significantly from advanced-stage patients (p = 0.014 and p = 0.00 6 for IFN alpha 2 beta and IL-2, respectively). No relationship was ob served between in vitro responsiveness of cytotoxic cells to lymphokin e incubation and serum estradiol levels. We conclude that immunoendocr ine modulation is important in the development and progression of endo metriosis, as suggested by the strict relationship between natural kil ler activity and sevum estradiol levels in advanced stage disease. A p rimitive, intrinsic defect of immune reactivity seems to be excluded b y the preserved in vitro responsiveness of cytotoxic cells to lymphoki ne incubation.