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

The in vitro effect of phenytoin (PHT) on the production of interleukin-g ( IL-6) and interleukin-8 (IL-8) in human gingival fibroblasts, challenged wi th or without interleukin-1 beta (IL-1 beta), was studied. PHT (20 mu g/ml) alone increased the mRNA level for both IL-6 and IL-8, as well as synergis tically enhancing the production of IL-6 and IL-8, at both transcriptional and translational level in fibroblasts challenged with IL-1 beta (30 pg/mi) . The stimulatory effect of PHT on IL-1 beta-induced IL-6 produc tion was s trongly reduced by the specific cyclooxygenase-2 inhibitor NS-398 (1 mu M). The anti-inflammatory drug, dexamethasone (1 mu M), abolished the producti on of both IL-6 and IL-8 in gingival fibroblasts challenged with PHT in the presence or absence of IL-1 beta. The ability of PHT, alone as well as in combination with IL-l, to upregulate the production of IL-6 and IL-8 in hum an gingival fibroblasts may contribute to enhanced recruitment and activati on of inflammatory cells. This effect of PHT may thereby give a prerequisit e for the establishment of an interaction between cytokines and connective tissue cells in the periodontal tissue, which is suggested to lead to gingi val overgrowth.