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 conflicting theories have been proposed to explain the 
fibroblast's function in CsA-induced gingival overgrowth. The aim of this study 
is to assess the proliferation of gingival fibroblasts 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 fibroblast 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 Modified Eagle Medium (DMEM) containing 10% fetal bovine 
serum (FBS), Streptomycin and Penicillin. The samples were cultured in 25 cm(2) 
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-1β, IL-6, 
IL-8, TNF-α, and TGF-β1 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 significantly higher levels of IL-6, IL-8 and TGF-β1 in 
adult gingival fibroblasts than it did in the control group; whereas, the 
expression of IL-1β and PGE2 in the fibroblasts exposed to CsA was significantly 
weaker (P < 0.05). The fibroblasts in the two groups did not reveal any 
noticeable difference in the production of TNF-α. Furthermore, cell 
proliferation in the CsA group was not significantly higher than that in the 
control group. No significant differences in cytokines TNF-α and IL-1β were 
noted between the two groups. The results indicated that CsA stimulated cell 
proliferation in the pediatric fibroblast cell line. Comparison between the 
results in the adult and pediatric groups demonstrated that the levels of IL-1β, 
IL-6, IL-8, and PGE2 were significantly higher in the pediatric group than in 
the adult group; however, statistics showed no significant difference in the 
levels of TNF-α and TGF-β1 and CsA-induced proliferation between these two 
groups.
CONCLUSIONS: The mechanism of a CsA-induced fibroblast overgrowth may converge 
on the steps involving fibroblast proliferation and cytokine network including 
IL-6, IL-8, IL-1β, TGF-β1, and PGE2, in both adults and pediatrics. As the 
prevalence and intensity of drug-induced gingival overgrowth is more serious in 
the pediatrics. As group than in adults, we suggest that more studies be 
conducted on the pediatric group.