MACROPHAGE-DERIVED CYTOKINES IN THE FOLLICULAR FLUIDS OF WOMEN WITH INFERTILITY DUE TO IMMUNOLOGICAL CAUSES - ELEVATED LEVELS OF INTERLEUKIN-6 AND LOW-LEVELS OF GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR

The cytokines are (glyco)proteins secreted by lymphoid and non-lymphoi d cells which modulate several biological responses including the ovar ian function, Interleukin (IL)-1 and tumour necrosis factor (TNF)-alph a suppress 17 beta-estradiol (E-2) and progesterone release from granu losa and luteal cells in vitro, TNF-alpha affects negatively folliculo genesis and ovarian maturation, Additional in vivo evidence for a role of this macrophage-derived cytokine came from our recent observation that women with infertility due to immunological causes have elevated intrafollicular fluid levels of TNF-alpha and decreased levels of E-2 compared to women with a tubal factor of infertility, Because the macr ophages are a primary component of the intrafollicular compartment, th e present study was undertaken to evaluate whether other macrophage-de rived cytokines are also released in the human follicular fluid, To ac complish this, we measured the levels of IL-1 beta, IL-6, IL-10 and gr anulocyte-macrophage colony-stimulating factor (GM-CSF) in the follicu lar fluids of two groups of infertile women undergoing to an in vitro fertilization program, The first group of women had a significant titr e of anti-spermatozoon antibodies in the serum end/or the mucus as the only cause of infertility, whilst the second group of women was infer tile because of non patent fallopian tubes. Intrafollicular cytokines levels were measured by solid-phase ELISA and steroid concentrations b y radioimmunoassay. Whilst IL-1 beta, IL-6, IL-10, and GM-CSF were all measurable in the follicular fluid of both groups of women, the level s of IL-6 were found to be significantly more elevated and those of GM -CSF lower in patients with infertility due to immunological causes as compared to those with tubal infertility. The former had also decreas ed intrafollicular E-2 levels and increased progesterone concentration s. No difference was seen in the follicular fluid levels of testostero ne and androstenedione. In conclusion, several macrophage-derived cyto kines are present in the follicular fluids of infertile women. Patient s with infertility due to immunological causes had higher levels of IL -6 and lon er concentrations of GM-CSF as compared to patient,vith a t ubal factor of infertility. We speculate that this abnormal cytokine p rofile may contribute to the altered intrafollicular steroid milieu. ( C) 1998 Academic Press.