Cyclooxygenase‐2 Inhibitors Decrease Interleukin‐1β–Stimulated Prostaglandin E 2 and IL‐6 Production by Human Gingival Fibroblasts

Background: Previous work showed that normal and aggressive periodontitis (AgP) gingival fibroblasts produce the boneresorbing cytokine IL‐6. PGE 2 is important in regulating IL‐6 production. Non‐steroidal anti‐inflammatory drugs inhibit PG synthesis via COX‐1 and/or COX‐2 isoenzymes and may inhibit periodontal destruction. COX‐2 is induced after cellular activation (i.e., by inflammatory cytokines such as IL‐1β). Little is known about IL‐1β‐stimulated AgP fibroblast IL‐6 and PGE 2 production and their regulation by COX inhibitors. The objective of this study was to determine the effects of COX‐2 inhibitors on amounts of PGE 2 and IL‐6 made by IL‐1β‐stimulated gingival fibroblasts. Methods: Gingival fibroblasts (2.5 × 10 4 ) from healthy or severe periodontitis patients were cultured in serum‐free medium, with or without IL‐1β (10 –11 M) for 24 hours, with or without the COX‐1/2 inhibitor indomethacin or the selective COX‐2 inhibitors NS‐398, celecoxib, or rofecoxib. PGE 2 and IL‐6 in culture supernatants were determined by specific enzyme‐linked immunosorbent assay (ELISA)s. Results: All of the COX inhibitors caused dose‐dependent decreases in IL‐1β‐stimulated PGE 2 , to a maximum of >90% in all cell lines ( P ≤0.0001). The selective COX‐2 inhibitors, but not indomethacin, caused partial (generally up to approximately 60%), dose‐dependent decreases in IL‐1β‐stimulated IL‐6 in all cell lines ( P ≤0.003). When exogenous PGE 2 was added concurrently with COX‐2 inhibitors before addition of IL‐1β, IL‐6 production returned to levels at or approaching that produced by cells exposed only to IL‐1β ( P ≤0.04). Conclusion: The results suggest that COX‐2 inhibition may be useful in helping to control fibroblast production of IL‐6 in patients with severe periodontitis. J Periodontol 2003;74:1754‐1763 .