Influence of Cyclosporin A on human gingival keratinocytes in vitro.
OBJECTIVE
Gingival hyperplasia is a well known side effect of Cyclosporine A therapy. The aetiology of this is not totally understood and there is debate whether it is hyperplasia of the gingival epithelium or of the submucosal connective tissue, or both, and what roles play factors like age and gender of the patients, duration and dosage of the drug.


METHODS
The influence of different Cyclosporine A concentrations (10(-6) g/ml; 5 x 10(-7) g/ml; 10(-9) g/ml) and of no medication (controls) on growth and proliferation of cultured human gingival keratinocytes was investigated after a culture period of 3, 6 and 9 days. Cell proliferation was assessed by counting anti Ki-67 stained nuclei, cell growth by counting total number of nuclei and by the EZ4U-assay.


RESULTS
There was no significant correlation of the cell proliferation rate and cellular growth with either gender (p > 0.568) or duration of medication (p > 0.876); but Cyclosporine A concentration showed a highly significant influence on cellular growth (p = 0.0001). Inhibition of cell growth was dependent on drug dosage, but a low concentration of 10(-9) g/ml even stimulated cell growth.


CONCLUSIONS
There is evidence that Cyclosporine A in low concentrations (10(-9) g/ml as applied in long-term therapy) stimulates gingival keratinocyte growth and therefore might be related to hyperplasia of the gingiva. However, high Cyclosporine A concentrations may inhibit cell growths and factors like gender of the patient did not show any influence in-vitro.
Lauer
Günter
G
Department of Oral and Maxillofacial Surgery, University Hospital Carl Gustav Carus, Technical University Dresden, Germany. guenter.lauer@uniklinikum-dresden.de
Mai
Ronald
R
Pradel
Winnie
W
Proff
Peter
P
Gedrange
Tomas
T
Beyer
Jan
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D005881:Gingiva / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D005885:Gingival Hyperplasia / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D012737:Sex Factors
D007166:Immunosuppressive Agents; D019394:Ki-67 Antigen; D016572:Cyclosporine