Evidence that cyclosporine inhibits periodontal prostaglandin I2 synthesis.
Cyclosporine (CsA) is a selective immunosuppressant widely used in clinical therapy. Like phenytoin and nifedipine, the drug is associated with gingival overgrowth. This study considers the interaction of CsA and prostaglandin I2 (PGI2), in particular the action of the drug on gingival tissue in vitro and in vivo. The PGI2-synthesis of rat, rabbit and human gingival tissue was examined by bioassay. In vivo CsA-therapy reduces gingival PGI2-synthesis. The results furthermore show a dose-dependent inhibition of PGI2-synthesis by CsA (1-100 micrograms/ml) in vitro. PGI2-synthesis from in vivo CsA-pretreated probes was further dose-dependently diminished by in vitro addition of CsA. As PGI2 exerts an antiproliferative activity via cAMP-elevation, the drug-induced inhibition of PGI2 production is claimed to be responsible for gingival hyperplasia in CsA-treated patients.
Nell
A
A
Department of Conservative Dentistry, University of Vienna, Austria.
Matejka
M
M
Solar
P
P
Ulm
C
C
Sinzinger
H
H
D000328:Adult; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005260:Female; D005881:Gingiva / Q000187:drug effects* / Q000378:metabolism; D005885:Gingival Hyperplasia / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011464:Epoprostenol; D000242:Cyclic AMP