Effect of phenytoin on the production of interleukin-6 and interleukin-8 in human gingival fibroblasts

• Published in: Journal of oral pathology & medicine 2000-11, Vol.29 (10), p.491-499
• Main Authors: Modéer, T., Domeij, H., Andurén, I., Mustafa, M., Brunius, G.
• Format: Article
• Language: English
• Subjects: Adolescent; Anticonvulsants - pharmacology; Biological and medical sciences; Cells, Cultured; Child; Child, Preschool; Drug Synergism; Ent. Stomatology; Enzyme-Linked Immunosorbent Assay; Fibroblasts - drug effects; Fibroblasts - metabolism; Gingiva - cytology; Gingiva - drug effects; Gingiva - metabolism; gingival fibroblasts; Humans; IL-1β; IL-6; IL-8; In Situ Hybridization; Interleukin-1 - pharmacology; Interleukin-6 - biosynthesis; Interleukin-8 - biosynthesis; Interleukins - biosynthesis; Investigative techniques, diagnostic techniques (general aspects); Medical sciences; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; PGE2; phenytoin; Phenytoin - pharmacology; RNA, Messenger - analysis; Stimulation, Chemical; Up-Regulation
• ISSN: 0904-2512; 1600-0714
• DOI: 10.1034/j.1600-0714.2000.291003.x

: The in vitro effect of phenytoin (PHT) on the production of interleukin‐6 (IL‐6) and interleukin‐8 (IL‐8) in human gingival fibroblasts, challenged with or without interleukin‐1β (IL‐1β), was studied. PHT (20 μg/ml) alone increased the mRNA level for both IL‐6 and IL‐8, as well as synergistically enhancing the production of IL‐6 and IL‐8, at both transcriptional and translational level in fibroblasts challenged with IL‐1β (30 pg/ml). The stimulatory effect of PHT on IL‐1β‐induced IL‐6 production was strongly reduced by the specific cyclooxygenase‐2 inhibitor NS‐398 (1 μM). The anti‐inflammatory drug, dexamethasone (1 μM), abolished the production of both IL‐6 and IL‐8 in gingival fibroblasts challenged with PHT in the presence or absence of IL‐1β. The ability of PHT, alone as well as in combination with IL‐1, to upregulate the production of IL‐6 and IL‐8 in human gingival fibroblasts may contribute to enhanced recruitment and activation of inflammatory cells. This effect of PHT may thereby give a prerequisite for the establishment of an interaction between cytokines and connective tissue cells in the periodontal tissue, which is suggested to lead to gingival overgrowth.