Cytokine production by peripheral blood monocytes during the normal human ovulatory menstrual cycle

Abstract

Background: There is considerable evidence that hormone-driven changes resembling an inflammatory response occur in the vascular compartment during the menstrual cycle, and peripheral blood monocytes may be central in the process. We investigated whether there is a cyclical change in intrinsic production of pro-inflammatory cytokines by monocytes in the ovulatory menstrual cycle, and whether there is a circulating factor that influences the pattern of cytokine production in a cyclical manner. Methods: Monocytes were purified by density-gradient centrifugation followed by countercurrent centrifugal elutriation, from the blood of normal women (n = 10) pre- and post-ovulation. Monocytes were cultured under basal conditions with bacterial lipopolysaccharide (LPS), and to determine the effects of circulating factors, incubations were also conducted in the presence of autologous serum. Concentrations of interleukin (IL)-1α, IL-1β, IL-6, tumour necrosis factor (TNF)-α and IL-1 receptor antagonist (IL-1Ra) were measured by sandwich ELISA. Results: The majority of IL-1α and IL-1β was cell associated, while the other cytokines were almost entirely secreted. Basal levels of IL-1α, IL-1β, and TNF-α were significantly increased following ovulation, while there was no significant change in levels of secretion of IL-6 or IL-IRa. These effects were present in unstimulated cells, suggesting prior activation in vivo. Cytokine production was increased in response to LPS; however, there was no consistent effect of autologous serum. Conclusions: Intrinsic production of pro-inflammatory cytokines by monocytes is increased following ovulation.