Crevicular fluid interleukin-1beta, tumor necrosis factor-alpha, and interleukin-6 levels in renal transplant patients receiving cyclosporine A.
Cyclosporine A(CsA) is successfully used to prevent graft rejection in organ transplantation and in the treatment of various systemic diseases. CsA-induced gingival overgrowth (CsA GO) is one of the most important side effects of this drug. However, the pathogenesis of this side effect is still unclear. It has been postulated that CsA-induced alterations of cytokine levels in gingival tissues might play a role in the drug-induced gingival overgrowth. The purpose of the present study was to determine the levels of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and IL-6 in gingival crevicular fluid (GCF) samples from renal transplant patients receiving CsA therapy and exhibiting CsA GO. Sixteen renal transplant patients receiving CsA, 12 patients with gingivitis, and 11 periodontally healthy subjects were included in this study. Data were obtained on plaque index, papilla bleeding index (PBI), and hyperplastic index from each study site. GCF samples and clinical data were obtained from: 1) 2 sites exhibiting CsA GO (CsA GO+) and 2 sites not exhibiting CsA GO (CsA GO-) in each CsA-treated patient; 2) diseased sites in each patient with gingivitis; and 3) 2 healthy sites in each subject with clinically healthy periodontium. CsA GO+ and CsA GO- sites were also divided into 2 subgroups as clinically uninflamed (PBI = 0) and inflamed (PBI > or = 1). The total amounts of cytokines in GCF were assayed by enzyme-linked immunosorbent assay. GCF IL-1beta levels were significantly higher in CsA GO+ sites compared to CsA GO-sites. Higher GCF levels of IL-1beta and IL-6 were detected in diseased sites compared to healthy sites. Although GCF IL-1beta levels in CsA GO+ sites were significantly higher than in the diseased sites, IL-6 levels of these sites were lower than in the diseased sites, whereas clinical degrees of gingival inflammation were similar in CsA GO+ and diseased sites. Additionally, while IL-1beta and IL-6 levels were similar in uninflamed CsA GO- sites and healthy sites, IL-1beta levels were significantly higher in uninflamed CsA GO+ sites compared to healthy sites and uninflamed CsA GO- sites. However, IL-1beta and IL-6 levels were significantly higher in inflamed CsA GO- sites compared to uninflamed CsA GO+ sites. No significant changes in GCF TNF-alpha levels were found between the groups. These data indicate that CsA therapy does not increase IL-1beta and IL-6 levels in GCF directly and that gingival inflammation plays a significant role in the elevation of GCF IL-1beta and IL-6 levels. For this reason, it is suggested that the alterations of GCF IL-1beta and IL-6 levels in CsA-treated patients might be responsible for the CsA-induced gingival overgrowth not by itself but also in combination with other factors associated with inflammation. To our knowledge, this is the first report describing the levels of cytokines in GCF of CsA-treated patients. We believe that further studies will contribute to the description of the pathogenesis of CsA-induced gingival overgrowth.
Atilla
G
G
University of Ege, School of Dentistry, Department of Periodontology, Izmir, Turkey. atilla@dishekimligi.ege.edu.tr
Kütükçüler
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D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D016572:Cyclosporine / Q000009:adverse effects*; D016207:Cytokines / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005883:Gingival Crevicular Fluid / Q000737:chemistry; D005885:Gingival Hyperplasia / Q000139:chemically induced* / Q000209:etiology; D005891:Gingivitis / Q000150:complications / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D016207:Cytokines; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016572:Cyclosporine