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 inflamed gingival tissue and may play an important role in periodontal pathogenesis. Recent studies suggest that monocytic products, such as interleukin (IL)-1 beta, could stimulate IL-6 production by human gingival fibroblasts (HGF). In this context, the production of local cytokines and inflammatory mediators could regulate the secretory capacity of resident gingival fibroblasts. Therefore, the purpose of this study was to determine if PGE(2) induced by IL-1 beta could potentiate the IL-6 response by HGF. Utilizing an ELISA, it was determined that maximal IL-6 occurred when HGF were stimulated with 0.10-10 nM IL-1 beta. These concentrations of IL-1 beta also induced a small, but significant increase in PGE(2) production by HGF. Interestingly, the combination of IL gamma beta and PGE(2) induced a synergistic rise in IL-6 production by HGF. Moreover, inclusion of indomethacin caused a 20% reduction in IL-6 production and totally eliminated PGE(2) production. These findings provide additional rationale for the clinical use of NSAIDs in the management of periodontal disease due to their ability to attenuate production of both PGE(2), and IL-6. These results suggest the endogenous PGE(2) induced by IL-1 beta plays an important regulatory role in IL 6 production by HGF. Moreover, they support the concept that elevated PGE(2)induced during inflammation can regulate HGF secretory function.