Cyclooxygenase-2 Inhibitors Decrease Interleukin-1β–Stimulated Prostaglandin E2 and IL-6 Production by Human Gingival Fibroblasts

• Autores: Dr. David A. Tipton, Jon C. Flynn, Sidney H. Stein, Mustafa Kh. Dabbous
• Localización: Journal of periodontology, ISSN 0022-3492, Vol. 74, Nº. 12, 2003, págs. 1754-1763
• Idioma: inglés
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• Resumen

  • Background: Previous work showed that normal and aggressive periodontitis (AgP) gingival fibroblasts produce the boneresorbing cytokine IL-6. PGE2 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 PGE2 production and their regulation by COX inhibitors. The objective of this study was to determine the effects of COX-2 inhibitors on amounts of PGE2 and IL-6 made by IL-1β-stimulated gingival fibroblasts.

    Methods: Gingival fibroblasts (2.5 × 104) from healthy or severe periodontitis patients were cultured in serum-free medium, with or without IL-1β (10–11M) for 24 hours, with or without the COX-1/2 inhibitor indomethacin or the selective COX-2 inhibitors NS-398, celecoxib, or rofecoxib. PGE2 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 PGE2, 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 PGE2 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.