Progressive rise in the expression of interleukin-6 in human endometrium during menstrual cycle is initiated during the implantation window

In order to be prepared for implantation, human endometriumundergoes a predictable series of proliferative and secretorychanges. Cytokines play an important role in regulation of thesechanges. Therefore, in this study, we immunolocalized the cytokine,interleukin-6 (IL-6), its receptor and the signal transducergp130 in human endometrium throughout the menstrual cycle. Duringthe entire menstrual cycle, the IL-6 receptor and gp130 werefound primarily in the endometrial glands and to a lesser extentin the stroma. The immunoreactivity of these proteins did notchange in endometrial cells during the entire menstrual cyclewith an exception of reduced immunoreactivity of gp130 in endometrialglands during menstrual phase. Immunostaining showed that immunoreactiveIL-6 was weakly expressed in human endometrium during the proliferativephase. Strong immunoreactivity for IL-6 appeared in endometriumduring the putative 'implantation window'. Expression was byfar most pronounced both in the glandular and surface epithelialcells. The amount of immunoreactive IL-6 in the epithelium progressivelyincreased during the secretory/menstrual phases. During thelate secretory phase, only stromal cells in the upper functionalisexhibited immunoreactivity for IL-6. Western blot analysis corroboratedthe immunohistochemical data. Human endometrial IL-6 consistedof a protein with an apparent mobility of 26 kDa. The immunoreactiveband of IL-6 was weak in the proliferative phase. The expressionof this protein increased progressively during the secretory/menstrualphases. The findings show a cell-specific pattern of distributionfor immunoreactive IL-6 in human endometrium. The menstrualcycle-dependent expression of IL-6 suggests that this cytokinemay play a role in changes in endometrium that prepare thistissue for implantation and menstrual shedding.