CREVICULAR FLUID INTERLEUKIN-1-BETA, TUMOR-NECROSIS-FACTOR-ALPHA, ANDINTERLEUKIN-6 LEVELS IN RENAL-TRANSPLANT PATIENTS RECEIVING CYCLOSPORINE-A

CYCLOSPORINE A(CsA) rs SUCCESSFULLY used to prevent graft rejection in organ transplantation and in the treatment of various systemic diseas es. CsA-induced gingival overgrowth (CsA GO) is one of the most import ant side effects of this drug. However, the pathogenesis of this side effect is still unclear. It has been postulated that CsA-induced alter ations of cytokine levels in gingival tissues might play a role in the drug-induced gingival overgrowth. The purpose of the present study wa s to determine the levels of interleukin-1 beta (IL-1 beta), tumor nec rosis 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, 1 2 patients with gingivitis, and 11 periodontally healthy subjects were included in this study. Data were obtained on plaque index, papilla b leeding index (PBI), and hyperplastic index from each study site. GCF samples and clinical data were obtained from: 1) 2 sites exhibiting Cs A 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; a nd 3) 2 healthy sites in each subject with clinically healthy periodon tium. CsA GO+ and CsA GO- sites were also divided into 2 subgroups as clinically uninflamed (PBI = 0) and inflamed (PBI greater than or equa l to 1). The total amounts of cytokines in GCF were assayed by enzyme- linked immunosorbent assay. GCF IL-1 beta levels were significantly hi gher in CsA GO+ sites compared to CsA GO-sites. Higher GCF levels of I L-1 beta and IL-6 were detected in diseased sites compared to healthy sites. Although GCF IL-1 beta levels in CsA GO+ sites were significant ly 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-1 beta and IL-6 levels were similar in uninflamed CsA GO- s ites and healthy sites, IL-1 beta levels were significantly higher in uninflamed CsA GO+ sites compared to healthy sites and uninflamed CsA GO- sites. However, Il-lp and IL-6 levels were significantly higher in inflamed CsA GO- sites compared to uninflamed CsA GO+ sites. No signi ficant changes in GCF TNF-a levels were found between the groups. Thes e data indicate that CsA therapy does not increase IL-IP and IL-6 leve ls in GCF directly and that gingival inflammation plays a significant role in the elevation of GCF IL-1 beta and IL-6 levels. For this reaso n, it is suggested that the alterations of GCF IL-1 beta and IL-6 leve ls in CsA-treated patients might be responsible for the CsA-induced gi ngival overgrowth not by itself but also in combination with other fac tors associated with inflammation. To our knowledge, this is the first report describing the levels of cytokines in GCF of CsA-treated patie nts. We believe that further studies will contribute to the descriptio n of the pathogenesis of CsA-induced gingival overgrowth.