Effects of sex hormones on production of interleukin-1 by human peripheral monocytes

Background: Interleukin-l (IL-I) is a potent mediator of inflammation and is known to induce bone resorption. We studied the effects of sex hormones on the function of human monocytes and demonstrated that prostaglandin E-2 (PGE(2)) production was enhanced by progesterone and estradiol. As PGE(2) has been shown to suppress the production of IL-1 by monocytes, it was speculated 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 investigated. Methods: Mononuclear leukocytes were obtained from 22 healthy adults. Progesterone, 17-beta estradiol (estradiol), and testosterone were used as representative sex hormones. Monocytes were incubated at 37 degrees C in air with 5% CO2 for 24 hours in RPMI 1640 medium with sex hormones at the designated concentrations. LPS (Salmonella typhimurium) was used to stimulate the monocytes 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 radio-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 reduced both IL-1 alpha and IL-1 beta production. Progesterone also reduced IL-1 alpha and IL-1 beta production significantly at concentrations of 0.1 ng/ml or more and 0.02 ng/ml or more, respectively. The reductions in IL-1 alpha 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 from human peripheral monocytes. The inhibition was not the result of enhanced production of PGE(2). Under conditions in which sex hormone levels are low, monocytes produce IL-1 more readily in response to stimulation by LPS than high levels of such hormones. Low concentrations of sex hormones may be considered as one of the risk factors for periodontitis.