MODULATION BY PROGESTERONE OF INTERLEUKIN-6 PRODUCTION BY GINGIVAL FIBROBLASTS

THE GINGIVITIS ASSOCIATED WITH PREGNANCY has been attributed to increa sed concentrations of circulating estrogen and/or progesterone. Howeve r, the mechanism by which these steroids increase gingival inflammatio n is not known. Interleukin-6 (IL-6), a pleiotropic cytokine produced by many cell types including human gingival fibroblasts (hGF), is secr eted in response to inflammatory challenges such as bacterial lipopoly saccharide and interleukin-l (IL-1). This study tested the hypothesis that progesterone could modulate the local production of IL-6 by hGF. The effects of progesterone on IL-6 production were measured in vitro in serum-free, phenol red-free medium to eliminate possible effects of such medium additives. The concentration of IL-6 secreted into supern atant medium after a 24 hour challenge with IL-1 beta was estimated by radioimmunoassay. Total RNA from steroid-treated hGF was probed for I L-6 mRNA. In serum-free medium, progesterone dose-dependently and sign ificantly (P<0.05) inhibited IL-6 production by hGF, as did the glucoc orticoids hydrocortisone (HC) and dexamethasone. At progesterone conce ntrations common in late pregnancy, IL-6 production was reduced to lev els 40 to 50% of control. In addition, mRNA was significantly down-reg ulated by progesterone and HC, at both basal levels and after IL-1 bet a challenge. These results suggest that high levels of progesterone du ring pregnancy affect the development of localized inflammation by: do wn-regulation of IL-6 production, rendering the gingiva less efficient at resisting the inflammatory challenges produced by bacteria.