Effects of sex hormones on production of interleukin-1 by human peripheralmonocytes

Background: Interleukin-l (IL-I) is a potent mediator of inflammation and i s known to induce bone resorption. We studied the effects of sex hormones o n the function of human monocytes and demonstrated that prostaglandin E-2 ( PGE(2)) production was enhanced by progesterone and estradiol. As PGE(2) ha s been shown to suppress the production of IL-1 by monocytes, it was specul ated that sex hormones also modify the production of IL-1 by regulating PGE (2) production. Thus, the effects of sex hormones on the production of IL-1 from human peripheral monocytes and the influence of PGE(2) were investiga ted. Methods: Mononuclear leukocytes were obtained from 22 healthy adults. Proge sterone, 17-beta estradiol (estradiol), and testosterone were used as repre sentative sex hormones. Monocytes were incubated at 37 degrees C in air wit h 5% CO2 for 24 hours in RPMI 1640 medium with sex hormones at the designat ed concentrations. LPS (Salmonella typhimurium) was used to stimulate the m onocytes at a concentration of 10 mu g/ml. The concentrations of IL-1 alpha and IL-1 beta in the medium were determined by enzyme-linked immunosorbent assay kits. The concentration of PGE(2) was determined using a direct radi o-immunoassay kit. Indomethacin was used to inhibit the synthesis of PGE(2) and eliminate its effect on the production of IL-1. Results: Estradiol at concentrations of 0.04 ng/ml or more significantly re duced both IL-1 alpha and IL-1 beta production. Progesterone also reduced I L-1 alpha and IL-1 beta production significantly at concentrations of 0.1 n g/ml or more and 0.02 ng/ml or more, respectively. The reductions in IL-1 a lpha and IL-1 beta production by sex hormones were not affected by addition of indomethacin. Conclusions: Estradiol and progesterone inhibited the production of IL-I fr om human peripheral monocytes. The inhibition was not the result of enhance d production of PGE(2). Under conditions in which sex hormone levels are lo w, monocytes produce IL-1 more readily in response to stimulation by LPS th an high levels of such hormones. Low concentrations of sex hormones may be considered as one of the risk factors for periodontitis.