Cyclosporin A Regulates Interleukin‐1ßand Interleukin‐6 Expression in Gingiva: Implications for Gingival Overgrowth

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Abstract
Background: Gingival overgrowth is a common side effect following the administration of cyclosporin A (CsA); however, the cellular mechanisms remain poorly understood. CsA's immunosuppressant properties involve the regulation of synthesis and cellular response to cytokines. A CsA‐induced alteration in the cytokine profile within gingival tissue could provide a mechanism for gingival hyperplasia. The aim of this study was to investigate the effects of CsA on the production of 2 cytokines — interleukin‐1ß(IL‐1ß) and interleukin‐6 (IL‐6) — by both gingival fibroblasts and peripheral blood mononuclear cells (PBMC).Methods: Cells were stimulated for 24 hours in the presence of CsA over a concentration range of 100 to 2,000 ng/ml and the resultant cytokine production determined by ELISA. In addition, levels of both cytokines within normal, inflamed, and overgrown gingival tissue were determined.Results: CsA inhibited IL‐6 production by gingival fibroblasts in a dose‐dependent manner. In contrast, at a concentration of 2,000 ng/ml, CsA stimulated IL‐6 production by PBMC ( P< 0.05). Fibroblasts derived from overgrown gingiva produced significantly higher levels of IL‐6 than their normal counterparts ( P P Conclusions: These results show that CsA does regulate cytokine expression in gingival tissue. This effect may play an important role in the pathogenesis of CsA‐induced gingival overgrowth. J Periodontol 1999;70:294‐300.

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