PROSTAGLANDIN E(2) POTENTIATES INTERLEUKIN-1-BETA INDUCED INTERLEUKIN-6 PRODUCTION BY HUMAN GINGIVAL FIBROBLASTS

Increased levels of cytokines and prostanoids have been detected in in flamed gingival tissue and may play an important role in periodontal p athogenesis. Recent studies suggest that monocytic products, such as i nterleukin (IL)-1 beta, could stimulate IL-6 production by human gingi val fibroblasts (HGF). In this context, the production of local cytoki nes and inflammatory mediators could regulate the secretory capacity o f resident gingival fibroblasts. Therefore, the purpose of this study was to determine if PGE(2) induced by IL-1 beta could potentiate the I L-6 response by HGF. Utilizing an ELISA, it was determined that maxima l IL-6 occurred when HGF were stimulated with 0.10-10 nM IL-1 beta. Th ese concentrations of IL-1 beta also induced a small, but significant increase in PGE(2) production by HGF. Interestingly, the combination o f IL gamma beta and PGE(2) induced a synergistic rise in IL-6 producti on by HGF. Moreover, inclusion of indomethacin caused a 20% reduction in IL-6 production and totally eliminated PGE(2) production. These fin dings provide additional rationale for the clinical use of NSAIDs in t he management of periodontal disease due to their ability to attenuate production of both PGE(2), and IL-6. These results suggest the endoge nous PGE(2) induced by IL-1 beta plays an important regulatory role in IL 6 production by HGF. Moreover, they support the concept that eleva ted PGE(2)induced during inflammation can regulate HGF secretory funct ion.