Proliferative and inductive effects of cyclosporin a on gingival fi broblast of child and adult

Abstract

Background: Gingival overgrowth is a serious side-effect that accompanies the use of Cyclosporin A (CsA). Up to 97% of the transplant recipient children, who were submitted to CsA therapy, have been reported to suffer from this side-effect. Several confl icting theories have been proposed to explain the fi broblast’s function in CsA-induced gingival overgrowth. The aim of this study is to assess the proliferation of gingival fi broblasts and levels of released cytokines after being exposed to CsA, in both adults and pediatric groups, and to make a comparison between the results of the two groups.

Materials and Methods: The adult fi broblast samples were derived from four healthy adults, aged 35 to 42 years and pediatric samples were obtained from four healthy children, age between four and eleven years. Tissue samples were plated in Dulbecco’s Modifi ed Eagle Medium (DMEM) containing 10% fetal bovine serum (FBS), streptomycin, and penicillin. The samples were cultured in 25 cm2 plates containing 5% CO2, and incubated at 37°C. The cells used for all the experiments were at the fourth passage. The concentration of PGE2, IL-1â, IL-6, IL-8, TNF-á, and TGF-â1 was determined by the enzyme-linked immunosorbent assay (ELISA) and the proliferation rate was assessed by the MTT assay. Alpha error levels were set as 0.05.

Results: CsA stimulated signifi cantly higher levels of IL-6, IL-8, and TGF-â1 in adult gingival fi broblasts than it did in the control group; whereas, the expression of IL-1â and PGE2 in the fi broblasts exposed to CsA was signifi cantly weaker (P < 0.05). The fi broblasts in the two groups did not reveal any noticeable difference in the production of TNF-á. Furthermore, cell proliferation in the CsA group was not signifi cantly higher than that in the control group. No signifi cant difference in cytokines TNF-á and IL-1â were noted between the two groups. The results indicated that CsA stimulated cell proliferation in the pediatric fi broblast cell line Comparison between the results in the adult and pediatric groups demonstrated that the levels of IL-1â, IL-6, IL-8, and PGE2 were signifi cantly higher in the pediatric group than in the adult group; however, statistics showed no signifi cant difference in the levels of TNF-á and TGF-â1 and CsA-induced proliferation between these two groups.

Conclusions: The mechanism of a CsA-induced fi broblast overgrowth may converge on the steps involving fi broblast proliferation and cytokine network including IL-6, IL-8, IL-1â, TGF-â1, and PGE2, in both adults and pediatrics. As the prevalence and intensity of drug-induced gingival overgrowth is more serious in the pediatric group than in adults, we suggest that more studies be conducted on the pediatric group.

Key Words: Cyclosporin, gingival hyperplasia, fi broblasts, Phenytoin