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Human Reproduction, Vol. 14, No. 1, 162-166, January 1999
© 1999 European Society of Human Reproduction and Embryology

Cytokines in the follicular fluid of stimulated and non-stimulated human ovaries; is ovulation a suppressed inflammatory reaction?

U. Büscher1,4, F.C.K. Chen1, H. Kentenich2 and H. Schmiady3

1 Klinik für Geburtsmedizin, Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353 Berlin, 2 Frauenklinik, DRK-Kliniken-Westend and 3 Klinik für Frauenheilkunde und Geburtshilfe, Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universität zu Berlin, Germany

We determined the concentrations of tumour necrosis factor (TNF)-{alpha}, interleukins (IL)-1ß, -6, -8 and -1-receptor antagonist (IL-1-ra) and of oestradiol and progesterone in the follicular fluid of 111 women undergoing in-vitro fertilization (IVF) and of six women with ovarian cysts in order to elucidate mid-cycle mechanisms causing dissociation of the follicle wall and local rupture of the ovarian tissue complex. Four stimulation protocols were administered: gonadotrophin releasing hormone agonist/human menopausal gonadotrophin (GnRHa/HMG), clomiphene citrate/HMG (CC/HMG), HMG and follicle-stimulating hormone (FSH). Concentrations of TNF{alpha} and IL-1ß were below 15 and 3 pg/ml respectively. IL-6 (median 4.1, 3.5–4.4 pg/ml, 95% CI) was higher after stimulation with FSH (5.6 pg/ml) than with HMG (3.2 pg/ml, P < 0.05) or GnRHa/HMG (3.7 pg/ml, P < 0.05), and after stimulation with CC/HMG (5.5 pg/ml) than with HMG (P < 0.01) or GnRHa/HMG (P < 0.001). IL-8 ranged from 32 to 1241 pg/ml (147, 117–178 pg/ml) and IL-1-ra from <31 to >10 000 pg/ml (156, 109–192 pg/ml). Cytokine levels did not correlate to oestradiol or progesterone concentrations. The ovarian cysts contained similar IL-8 (14–540 pg/ml) and IL-1ß (<30 pg/ml), but higher IL-6 (13.6–>500 pg/ml) and lower IL-1-ra concentrations. We assume that IL-6, IL-8 and IL-1-ra are involved in peri-ovulatory cellular interactions. Thus, ovulation appears to be a cytokine-regulated process of an `inflammation' (IL-6 and IL-8) followed by `anti-inflammatory' reactions (IL-1-ra).

Key words: follicular fluid/interleukin-6/interleukin-8/interleukin-1 receptor antagonist/ovulation physiology

4 To whom correspondence should be addressed


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