Matrix metalloproteinases (MMP-8 and-9) and neutrophil elastase in gingival crevicular fluid of cyclosporin-treated patients

Background: Gingival overgrowth (GO) is one of the most important side effe cts of cyclosporin A (CsA) medication, but its pathogenesis is not complete ly understood. The aim of this study was to identify and compare collagenas e-2 (MMP-8), gelatinase-B (MMP-9), and neutrophil (PMN)-elastase levels in gingival crevicular fluid (GCF) from 15 renal transplant patients receiving CsA therapy and exhibiting CsA GO, 14 patients with gingivitis, and 10 per iodontally healthy subjects. Methods: Clinical data were obtained on plaque index, papilla bleeding inde x, and hyperplastic index from each site studied. GCF samples and clinical data were collected from: 2 sites exhibiting CsA GO (CsA GO+) and 2 sites n ot exhibiting CsA GO (CsA GO-) in each CsA-treated patient; 2 diseased site s in each patient with gingivitis; and 2 healthy sites in each subject with clinically healthy periodontium. CsA GO+ and CsA GO- sites were divided in to 2 sub-groups as clinically not inflamed (PBI = 0) and inflamed (PBI grea ter than or equal to1). GCF MMP-8, MMP-9, and PMN-elastase levels were anal yzed by immuno-fluorometric assay. Results: GCF MMP-8 and -9 levels and clinical degrees of gingival inflammat ion in CsA GO+ sites were similar to those in diseased sites. However, GCF elastase levels were significantly lower in CsA GO+ sites compared to those in diseased sites. GCF MMP-8, -9 and PMN-elastase levels were not differen t between CsA GO- sites and healthy sites. Additionally, GCF MMP-8 and -9 l evels in inflamed CsA GO+ sites were higher but not statistically significa ntly than those in diseased sites. In contrast, GCF PMN-elastase levels in inflamed CsA GO+ sites were significantly lower than the levels in diseased sites. Conclusions: These results show that CsA therapy does not have a significan t effect on GCF MMP-8 and MMP-9 levels, but the gingival inflammation seems to be the main reason for their elevations. However, low GCF PMN-elastase levels can be an important factor in the pathogenesis of CsA-induced gingiv al overgrowth. CsA therapy does not eliminate the potential use of GCF MMP- 8 and -9 as future diagnostic markers of gingival inflammation.