Effects of selected immunouppressive drugs on prostaglandin release, protein synthesis and cell proliferation in human gingival fibroblasts and on the growth of plaque bacteria.
BACKGROUND
Immunosuppressants play an essential role in transplantation therapy. In view of the side effects, e.g. gingival overgrowth, the present in vitro study was performed in order to investigate the effect of selected immunosuppressants on metabolic activities of gingival fibroblasts. Furthermore, the effect on the growth of six oral microorganisms was investigated.


METHODS
Human gingival fibroblasts were incubated in the presence of azathioprine (Aza), cyclosporin A (CsA), tacrolimus (Tac) or mycophenolatmofetil (Myc). PGE subset 2 release was determined by means of a specific competitive enzyme immunoassay, using monoclonal antibodies specific for PGE subset 2 (clone E2R1). The protein content was measured spectrophotometrically. A redox indicator system was employed to assess the proliferation activity. In an additional trial the growth of six strains of oral bacteria (A. viscosus T14V, S. oralis H1, S. mutans 10449, C. gingivalis DR2001, A. actinomycetemcomitans Y4, and M. micros 33270) in the presence of the immunosuppressants was measured.


RESULTS
In comparison with the controls, the PGE subset 2 release was increased by 39.3% following incubation with Aza, and by 77.0% with CsA. The protein concentrations (1 g immunosuppressant / ml medium) were reduced by 26.0% for Aza and 17.0% for Myc. Furthermore, a drug-dependent inhibition in the cell proliferation rate was noted after an incubation period of 6 hours (Aza 70.7%, CsA 78.2%, Myc 69.8%, Tac 64.0%). The most pronounced growth-inhibiting effects were observed for CsA at values ranging from 21.0% (S. mutans 10449) to 48.6% (A. viscosus T14V) growth inhibition.


CONCLUSIONS
The present study with common immunsuppresants demonstrated both a medication- and dose-dependent alteration in the metabolic activity of gingival fibroblasts. Furthermore, growth-inhibitory effects on the selected bacterial strains could be observed.
Pistorius
A
A
Department for Operative Dentistry, Johannes Gutenberg University Mainz, Augustusplatz 2, D-55131 Mainz, Germany.
Willershausen
B
B
Callaway
A
A
D016924:Actinomyces viscosus / Q000187:drug effects / Q000254:growth & development; D016976:Aggregatibacter actinomycetemcomitans / Q000187:drug effects / Q000254:growth & development; D001379:Azathioprine / Q000494:pharmacology*; D002206:Capnocytophaga / Q000187:drug effects / Q000254:growth & development; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D003773:Dental Plaque / Q000382:microbiology*; D015232:Dinoprostone / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D010462:Peptostreptococcus / Q000187:drug effects / Q000254:growth & development; D014176:Protein Biosynthesis; D013295:Streptococcus mutans / Q000187:drug effects / Q000254:growth & development; D016559:Tacrolimus / Q000494:pharmacology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D015232:Dinoprostone; D001379:Azathioprine; D016559:Tacrolimus