Background: Interleukin-1 (IL-1) 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 E2 (PGE2) production was enhanced by progesterone and estradiol. As PGE2 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 PGE2 production. Thus, the effects of sex hormones on the production of IL-1 from human peripheral monocytes and the influence of PGE2 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 microg/ml. The concentrations of IL-1alpha and IL-1beta in the medium were determined by enzyme-linked immunosorbent assay kits. The concentration of PGE2 was determined using a direct radio-immunoassay kit. Indomethacin was used to inhibit the synthesis of PGE2 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-1alpha and IL- 1beta production. Progesterone also reduced IL-1alpha and IL-1beta production significantly at concentrations of 0.1 ng/ml or more and 0.02 ng/ml or more, respectively. The reductions in IL- 1alpha and IL-1beta production by sex hormones were not affected by addition of indomethacin.
Conclusions: Estradiol and progesterone inhibited the production of IL-1 from human peripheral monocytes. The inhibition was not the result of enhanced production of PGE2. Under conditions in which sex hormone levels are low, monocytes produce IL- 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.