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Effect of phenytoin on interleukin‐1β production in human gingival fibroblasts challenged to tumor necrosis factor α in vitro
Author(s) -
Brunius Gustaf,
YucelLindberg Tülay,
Shinoda Keiji,
Modéer Thomas
Publication year - 1996
Publication title -
european journal of oral sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.802
H-Index - 93
eISSN - 1600-0722
pISSN - 0909-8836
DOI - 10.1111/j.1600-0722.1996.tb00042.x
Subject(s) - phenytoin , tumor necrosis factor alpha , prostaglandin e2 , chemistry , prostaglandin e , cytokine , interleukin , in vitro , pharmacology , flurbiprofen , prostaglandin , endocrinology , medicine , biochemistry , epilepsy , psychiatry
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 E 2 (PGE 2 ) 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 PGE 2 formation. When PHT and TNFα were added simultaneously, the drug potentiated the stimulatory effect of TNFα on both IL‐Iβ production and PGE 2 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 PGE 2 formation in gingival fibroblasts may be an important link in the pathogenesis of gingival overgrowth induced by PHT.