Natural killer activity in stage III and IV endometriosis: impaired cytotoxicity and retained lymphokine responsiveness of natural killer cells

Our objective was to investigate the role of estrogens in the development and progression of endometriosis, and evaluate the in vitro boosting 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 endometriosis patients who underwent laparoscopy for pelvic pain, infertility and benign adnexal masses, and it was correlated with serum estradiol levels. Twenty-five women with moderate and severe disease were re-evaluated for immune and endocrine parameters 4-8 weeks after surgery, before any specific adjuvant medical treatment, and analyzed for in vitro responsiveness of cytotoxic cells to interferon (IFN) alpha 2 beta and interleukin-2 (IL-2) incubation. Patients with moderate and severe 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 representation of natural killer cells, and persisted after surgical removal of all macroscopic endometriosis foci. A significant inverse relationship was observed between natural killer activity and serum estradiol levels, 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 cytotoxic cells to lymphokine incubation was preserved; both IFN alpha 2 beta and IL-2 were able to increase the cytotoxicity of natural killer cells significantly from advanced-stage patients (p = 0.014 and p = 0.006 for IFN alpha 2 beta and IL-2 respectively).(ABSTRACT TRUNCATED AT 250 WORDS)