Phenytoin induces interleukin-1 production in vitro
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T Modéer1, J Karsten, A Weintraub
1Department of Pedodontics, Odontological Clinics, Huddinge, Sweden.
Abstract:
Human adherent mononuclear cells and subcloned cell lines established from the human histiocytic cell line U-937 were cultured with phenytoin (PHT) and/or lipopolysaccharide (LPS) purified from Bacteroides fragilis. After the cultivation period, the cell-free supernatants were tested for interleukin-1 (Il-1) activity. The results showed that PHT induces Il-1 activity and potentiates LPS-induced Il-1 production. In the monocytic cell line U-937, the induced Il-1 production was found to be clonally distributed indicating that the response to PHT may be exerted by a subpopulation of monocytes. The PHT-induced Il-1 activity may be of importance in the development of gingival overgrowth. The induced Il-1 could also contribute to other known side effects such as dermatologic reactions accompanied by transient fever seen in patients medicating the drug.
Insights
Phenytoin (PHT) stimulates interleukin-1 (IL-1) production in human monocytes and enhances lipopolysaccharide (LPS)-induced IL-1. This PHT-induced IL-1 may contribute to adverse drug reactions like gingival overgrowth and fever.
Area of Science:
- Immunology
- Pharmacology
Background:
- Phenytoin (PHT) is an anticonvulsant drug with known side effects.
- Interleukin-1 (IL-1) is a key cytokine involved in inflammatory processes.
Purpose of the Study:
- To investigate the effect of PHT on IL-1 production in human monocytes.
- To explore the role of PHT-induced IL-1 in adverse drug reactions.
Main Methods:
- Human adherent mononuclear cells and U-937 cell lines were cultured with PHT and/or lipopolysaccharide (LPS).
- Cell-free supernatants were analyzed for IL-1 activity.
Main Results:
- PHT alone induced IL-1 activity.
- PHT potentiated LPS-induced IL-1 production.
- IL-1 production in response to PHT was clonally distributed in U-937 cells, suggesting a subpopulation of monocytes is responsible.
Conclusions:
- PHT can induce IL-1 production, potentially contributing to gingival overgrowth.
- PHT-induced IL-1 may also play a role in other side effects like fever and dermatologic reactions.