Cyclosporin but not tacrolimus significantly increases salivary cytokine contents in rats.
BACKGROUND
Cyclosporin (CsA) and tacrolimus (FK-506) are immunosuppressive drugs that specifically inhibit T-cell activation via calcineurin inhibition. Gingival overgrowth is a common side effect following the administration of CsA. The severity of gingival overgrowth seen in patients taking FK-506 is less than that observed with CsA. Little is known about the involvement of saliva in drug-induced gingival overgrowth. The purpose of this study was to investigate the salivary contents of tumor growth factor beta1 (TGF-beta1), epidermal growth factor (EGF), and interleukin-6 (IL-6) as well as the hystometry of gingival tissue obtained from rats treated with either FK-506 or CsA.


METHODS
For 30 or 60 days rats received daily subcutaneous injection doses of either CsA or FK-506 (10 mg/kg). The concentrations of TGF-beta1, EGF, and IL-6 in saliva were determined by enzyme-linked immunosorbent assay, and after histological processing, the oral epithelium and connective tissue were assessed at the region of the lower first molars.


RESULTS
The levels of TGF-beta1, EGF, and IL-6 in saliva were not significantly altered by any of the treatments after 30 days. After 60 days of treatment with CsA, gingival overgrowth and significant increase in salivary TGF-beta1, EGF, and IL-6 concentrations were observed; no statistically significant changes were induced by FK-506.


CONCLUSIONS
Within the limits of this experimental study, it can be concluded that CsA, but not FK-506, induced gingival overgrowth associated with an increase of the salivary levels of the cytokines TGF-beta1, EGF, and IL-6.
Spolidorio
Luís Carlos
LC
Department of Pathology, Dental School of Araraquara, State University of São Paulo (UNESP), Araraquara, SP, Brazil. lcs@foar.unesp.br
Holzhausen
Marinella
M
Spolidorio
Denise M Palomari
DM
Nassar
Carlos A
CA
Nassar
Patricia O
PO
Muscará
Marcelo Nicolás
MN
D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000032:analysis; D019214:Gingival Overgrowth / Q000139:chemically induced / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012463:Saliva / Q000378:metabolism*; D016559:Tacrolimus / Q000009:adverse effects*; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1
D016207:Cytokines; D007166:Immunosuppressive Agents; D015850:Interleukin-6; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D004815:Epidermal Growth Factor; D016572:Cyclosporine; D016559:Tacrolimus