Publicação: Cyclosporin but not tacrolimus significantly increases salivary cytokine contents in rats
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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.
