NATURAL CYTOTOXICITY AND GNRH AGONIST ADMINISTRATION IN ADVANCED ENDOMETRIOSIS - POSITIVE MODULATION ON NATURAL-KILLER ACTIVITY

Objective: To investigate the effects of pharmacologic suppression of ovarian function on the immune system, with respect to the clinical ou tcome of endometriosis and the possibility of an immunoendocrine combi ned treatment. Methods: After informed consent, 25 of 37 patients with revised American Fertility Society stage III and IV endometriosis who underwent postoperative medical treatment were selected and enrolled for this immunoendocrine longitudinal study. Medical treatment consist ed of tryptorelinum depot injection, 3.75 mg/month for 24 weeks. Blood samples were collected before the first injection in the early follic ular phase, day 2-3 of the cycle, and during medical treatment (every 4 weeks) and follow-up (every 6 months). At the end of the study, we h ad ten blood samples per patient to evaluate the cytotoxic activity, t he number of natural killer cells, and the serum levels of estradiol. Natural killer activity was determined against the K562 cell line by t arget cell retention of the fluorescent dye carboxyfluorescein diaceta te. Results: A positive immunomodulating effect was observed during Gn RH agonist administration. In particular, a significant progressive in crease in natural killer cell activity was defined within the first 12 weeks of medical treatment; after three injections, we observed the h ighest values of cytotoxicity, with a median of 7.1 lytic units (range 0.3-14.0; P =.02). Natural cytotoxicity then decreased toward a plate au, which persisted during therapy completation and follow-up, with sl ight fluctuations. In patients who had recurrence, the values of natur al killer cell activity were constantly lower than those in patients w ith disease-free follow-up, particularly within the first 12 weeks of medical treatment. Conclusion: This study showed a positive modulation of natural killer cell activity during the first 12 weeks of GnRH ago nist treatment in patients with advanced endometriosis. In particular, a relationship was suggested between natural cytotoxicity and clinica l outcome.