CYCLOSPORINE-A UP-REGULATES INTERLEUKIN-6 GENE-EXPRESSION IN HUMAN GINGIVA - POSSIBLE MECHANISM FOR GINGIVAL OVERGROWTH

CYCLOSPORINE A (CSA) IS A WIDELY USED IMMUNOSUPPRESSANT for transplant patients and is also used for the treatment of a wide variety of syst emic diseases with immunologic components. A prominent side effect of CsA administration is gingival overgrowth. It has been postulated that CsA alters fibroblast activity through effects on various cytokines s uch as the interleukins, however, as yet, data concerning the molecula r mechanisms involved in connective tissue proliferation are still pre liminary in nature. The purpose of this study was to evaluate interleu kin-6 (IL-6) gene expression in gingival tissues of patients receiving CsA therapy and exhibiting gingival overgrowth. Radioimmunoassay (RIA ) demonstrated a significant difference in tissue levels of IL-6 as me an +/- SEM. IL-6 content in CsA-stimulated tissue was 184.3 +/- 30.2 n g/mg total protein versus 23.3 +/- 6.5 ng/mg total protein in control tissue. In situ hybridization indicated that overgrown gingival tissue s from patients taking CsA had a significantly higher content of IL-6 mRNA when compared to control tissues. Expressing IL-6 mRNA levels as silver grains/cell, CsA-stimulated tissue had 166.9 +/- 12.0 grains of IL-6 mRNA/cell while control tissue had 12.8 +/- 3.0 grains of IL-6 m RNA/cell. These results demonstrate that CsA therapy results in increa sed levels of IL-6 protein and IL-6 mRNA in overgrown human gingival t issues. This is the first report of CsA-upregulated IL-6 gene expressi on in vivo, and may explain in part the molecular mechanisms responsib le for CsA-induced gingival overgrowth.