DYSREGULATION OF INTERLEUKIN-6 RESPONSES IN ECTOPIC ENDOMETRIAL STROMAL CELLS - CORRELATION WITH DECREASED SOLUBLE RECEPTOR LEVELS IN PERITONEAL-FLUID OF WOMEN WITH ENDOMETRIOSIS

Endometriosis (EM) is characterized by the aberrant growth of endometr ial cells at sites outside the uterus. We showed previously that perit oneal leukocyte interleukin-6 (IL-6) production is altered in women wi th EM relative to that in normal control women. Because studies sugges t that IL-6 may be growth regulatory for endometrial cells, we examine d IL-6 and IL-6 soluble receptor (IL-6sR) in the peritoneal fluid of 4 0 women. In addition, the growth responsiveness of ectopic endometrial stromal cells to IL-6 was evaluated. The severity of EM correlated wi th increased levels of IL-6 accompanied by decreased IL-6sR in periton eal fluid (controls, 1.0 +/- 0.1 and 525.4 +/- 53; stage I-II EM, 1.4 +/- 0.2 and 274.6 +/- 26; stage III-IV EM, 19.3 +/- 4.6 and 319.4 +/- 26; adhesions, 1.9 +/- 0.4 and 324.7 +/- 26 pmol/L IL-6 and IL-6sR, re spectively). Additional studies revealed that unstimulated endometrial stromal cells from ectopic implants secreted this cytokine in vitro. Furthermore, these cells were resistant to growth inhibition induced b y exposure to additional IL-6; this response correlated with weak expr ession of IL-6 receptor. Taken together, these findings lend further s upport to the hypothesis that dysregulation of IL-6 responses plays a role in the pathophysiology of EM.