Androgens modulate interleukin-6 production by gingival fibroblasts in vitro.
BACKGROUND
Pregnancy and puberty gingivitis have been attributed to increased concentrations of circulating sex hormones. This inflammatory gingival condition is accompanied by the local production of cytokines. The aims of this in vitro study were to assess, in the presence or absence of testosterone (T) or dihydrotestosterone (DHT), the production of interleukin-6 (IL-6) by human gingival fibroblasts (hGF), and to evaluate the effects of flutamide (a common anti-androgen) in this system.


METHODS
The effects of the androgens, T and DHT, on IL-6 production were measured in vitro in serum-free, phenol red-free medium. Cells were incubated with or without androgens for 72 hours; the concentration of IL-6 secreted into the medium after an additional 24-hour challenge with IL-1beta plus hormones was estimated by radioimmunoassay. The reverse transcription polymerase chain reaction was used to examine hGF and periodontal ligament cells (PDL) for the presence of androgen receptor.


RESULTS
In serum-free medium, T and DHT at concentrations of 5 x 10(-8) to 10(-7)M significantly (P <0.05) inhibited IL-6 production by hGF. Flutamide, up to concentrations of 2 x 10(-5)M, did not reverse this inhibition. The androgen receptor was identified in both hGF and PDL.


CONCLUSIONS
We concluded that elevated levels of androgens, specifically testosterone and dihydrotestosterone, could affect the stromal cell response to an inflammatory challenge by downregulation of IL-6 production. This in vitro study lends support to the hypothesis that increased hormones during pregnancy or puberty could modulate the development of localized inflammation.
Department of Periodontology, Medical College of Georgia, Augusta, GA 30912, USA.
R A
RA
Gornstein
C A
CA
Lapp
S M
SM
Bustos-Valdes
P
P
Zamorano
D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology / Q000502:physiology*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D013196:Dihydrotestosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005485:Flutamide / Q000494:pharmacology; D005881:Gingiva / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005891:Gingivitis / Q000276:immunology / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism; D011627:Puberty / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000502:physiology
D000726:Androgen Antagonists; D000728:Androgens; D017077:Culture Media, Conditioned; D015850:Interleukin-6; D013196:Dihydrotestosterone; D013739:Testosterone; D005485:Flutamide; D004247:DNA