ELEVATED INTERLEUKIN-6 LEVELS IN THE OVARIAN HYPERSTIMULATION SYNDROME - OVARIAN IMMUNOHISTOCHEMICAL LOCALIZATION OF INTERLEUKIN-6 SIGNAL

Objective: To examine the production and immunolocalization of interle ukin-6 (IL-6) in patients with the ovarian hyperstimulation syndrome. Methods: The study group consisted of patients with ovarian hyperstimu lation syndrome (n = 9) from whom serum and ascites samples were obtai ned. The control samples used were serum (n = 10) and peritoneal (n = 16) and follicular fluids (n = 8) from healthy individuals. Follicular fluid (n = 40) and serial serum samples were also obtained from patie nts undergoing menotropin stimulation for in vitro fertilization (IVF) before (n = 10) and after ovulation (n = 34). Interleukin-6 measureme nts were performed with a sensitive immunoassay and confirmed with a b ioassay. Immunohistochemical localization of IL-6 was performed with a mouse monoclonal antibody in normal premenopausal (n = 5) and postmen opausal ovaries (n = 5), as well as with cells from stimulated follicu lar fluid aspirates (n = 3). Results: We found significantly higher se rum and ascites IL-6 levels in ovarian hyperstimulation syndrome (mean 18.8 +/- 1.1 and 810.8 +/- 60.7 pg/mL, respectively) compared with po stovulatory serum and peritoneal fluid from normal controls (mean 4.4 +/- .69 and 44.7 +/- 7.5 pg/mL, respectively) (P < .001) or serum afte r menotropin stimulation (13.1 +/- 1.1 pg/mL) (P < .001). At the time of ovulation, follicular fluid IL-6 levels (normal controls, mean 9 +/ - 2.1 pg/mL; menotropin stimulation, mean 10.1 +/- 4 pg/mL) were highe r than in preovulatory serum (normal controls, mean 4.5 +/- .8 pg/mL; menotropin stimulation, mean 6.3 +/- 1.4 pg/mL) (P < .001). Immunohist ochemical localization of IL-6 revealed intense staining in corpora lu tea and theca cells from large antral follicles and luteinized granulo sa cells in follicular aspirates after menotropin stimulation. Conclus ion: Interleukin-6 levels are markedly elevated in the ovarian hyperst imulation syndrome when compared with controls. The higher follicular fluid IL-6 levels seen suggest local secretion of this cytokine. Immun ohistochemical correlation demonstrated IL-6 within ovarian theca cell s. These findings suggest a local role for IL-6 both in normal and sti mulated ovarian function. Whether IL-6 is directly responsible for the clinical manifestations of this syndrome is unclear. However, when pr oduced in massive amounts, the pro-inflammatory effects of IL-6 may co ntribute to its pathogenesis and perhaps serve as a marker for the dis ease.