Cyclosporin but not tacrolimus significantly increases salivary cytokine contents in rats
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Wiley
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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 β1 (TGF-β1), 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-β1, 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-β1, 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-β1, EGF, and IL-6 concentrations were observed; no statistically significant changes were induced by FK-506. Conclusion: 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-β1, EGF, and IL-6.
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Animal studies , Cyclosporin A/adverse effects , Gingival hyperplasia/etiology , Growth factors, epidermal , Growth factors, tumor β1 , Interleukin-6 , Saliva/analysis , Tacrolimus/adverse effects , cyclosporin , cytokine , epidermal growth factor , interleukin 6 , tacrolimus , transforming growth factor beta1 , animal experiment , animal model , animal tissue , concentration response , connective tissue , controlled study , enzyme linked immunosorbent assay , fibroblast , gingiva overgrowth , histometry , male , molar tooth , mouth mucosa , nonhuman , rat , salivation , Animals , Cyclosporine , Cytokines , Epidermal Growth Factor , Gingival Overgrowth , Immunosuppressive Agents , Male , Rats , Rats, Sprague-Dawley , Saliva , Tacrolimus , Transforming Growth Factor beta , Transforming Growth Factor beta1
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Journal of Periodontology, v. 76, n. 9, p. 1520-1525, 2005.
