Effect of phenytoin on interleukin-1β production in human gingival fibroblasts challenged to tumor necrosis factor αin vitro |
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| Authors: | Gustaf Brunius,Tü lay Yucel-Lindberg,Keiji Shinoda,Thomas Modé er |
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| Affiliation: | Department of Orthodontics and Pediatric Dentistry, Faculty of Odontology, Karolinska Institutet, Huddinge, Sweden;Department of Pediatric Dentistry, School of Dentistry, Asahi University, Gifu, Motosu-gun, Hozumi-cho501-02 Japan |
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| Abstract: | Effects and interaction of tumor necrosis factor α (TNFα) and the antiepileptic drug phenytoin (PHT) on interleukin-1β (IL-1β) production as well as on prostaglandin E2 (PGE2) formation were studied in gingival fibroblasts in vitro. TNFα, in contrast to PHT, dose-dependently stimulated the production of cell-associated IL-1β. The stimulatory effect of TNFα on IL-1β production was accompanied by enhanced PGE2 formation. When PHT and TNFα were added simultaneously, the drug potentiated the stimulatory effect of TNFα on both IL-Iβ production and PGE2 formation. The major PHT metabolite, p-HPPH, did not affect IL-1β production, either alone or in combination with TNFα. The production of IL-1β induced by TNFα and the combination of TNFα and PHT was further enhanced in the presence of the prostaglandin endoperoxide (PGH) synthase inhibitors, indomethacin and flurbiprofen. The PHT-mediated enhancement of TNFα-induced IL-1β production and PGE2 formation in gingival fibroblasts may be an important link in the pathogenesis of gingival overgrowth induced by PHT. |
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| Keywords: | gingival fibroblasts interleukin-1β phenytoin tumor necrosis factor |
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