Gender differences in IL-1α, IL-1β, and IL-1 receptor antagonist secretion from mononuclear cells and urinary excretion

Previous studies have reported increased secretion of IL-1-like activity from mononuclear cells and increased circulating levels during the luteal phase of the menstrual cycle. In this investigation, specific RIAs for the agonists IL-1α and IL-β as well as IL-1 receptor antagonist (IL-1Ra) were used to determine whether differential IL-1 secretory patterns exist between men and women or between phases of the menstrual cycle. Mononuclear cells were isolated from six men and five women at 4-h intervals from 8 am to 8 pm, with the women studied once in midfollicular phase and once in midluteal phase. In the absence of any intentional stimulation, significant differences in secretion were observed between groups (p < 0.03) for all three species of IL-1: women's cells isolated during the luteal phase secreted 5- to 10-fold more than cells from men, and women's cells isolated during the follicular phase secreted 13- to 28-fold more than cells from men. In addition, total 24-h urine samples were collected in intervals with end points coinciding with the blood samples. Urinary excretion correlated with cellular secretion for IL-β and IL-1Ra (p = 0.024 and 0.028, respectively), indicating that the in vitro results may correspond to differential processes occurring in vivo. Although greater absolute amounts of each species of IL-1 were secreted during the follicular phase, the ratio of agonist to antagonist secreted was greater in the luteal phase (p < 0.05), in agreement with previous studies of bioactivity. These results indicate that the regulation of IL-1 secretion is fundamentally different in women compared with men and alludes to the possibility that IL-1 may serve different biologic functions in women than men.