Abstract
Statins possess a wide variety of pleiotropic properties that are independent of their lipid-lowering abilities such as attenuating inflammation, oxidative stress, coagulation, platelet aggregation and stimulating bone formation. The aim of the study is to evaluate the effect of statins on clinical periodontal parameters and gingival crevicular fluid (GCF) levels of IL-1β, IL-10, and myeloperoxidase (MPO) in inflammatory periodontal diseases. Seventy-nine subjects with hyperlipidemia and 48 systemically healthy controls (C) were included. Hyperlipidemic patients were either given a diet (HD) or prescribed statin (HS). Patients were classified into three subgroups as those who were periodontally healthy (h), who had gingivitis (g), or who had chronic periodontitis (p). Blood samples were collected for the measurement of lipid profiles. Plaque index (PI), gingival index (GI), probing pocket depth (PD), clinical attachment level (CAL), and percentage of bleeding on probing (BOP) were recorded. Gingival crevicular fluid levels of IL-1β, IL-10, and MPO were measured in order to determine the anti-inflammatory and antioxidant effects of statins. Probing depth values of the HSp group were significantly lower than those of the Cp group. Percentage of BOP of the HSg group was significantly lower than those of the HDg and Cg groups. While the IL-1β level of the HSp group was significantly lower than that of the HDp group, IL-10 levels of the HSg group were significantly higher than those of the HDg group. MPO levels were significantly lower in the HSg group when compared to those in the HDg and Cg groups. Statin use decreased the IL-1β and MPO levels and enhanced IL-10 in GCF. It can be suggested that statins may attenuate periodontal inflammation and progression of periodontal inflammation.
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References
Genco, R.J. 1992. Host responses in periodontal diseases: current concepts. Journal of Periodontology 63: 338–55.
Okada, H., and S. Murakami. 1998. Cytokine expression in periodontal health and disease. Critical Reviews in Oral Biology and Medicine 9: 248–66.
Loos, B.G., J. Craandijk, F.J. Hoek, P.M. Wertheim-van Dillen, and U. van der Velden. 2000. Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients. Journal of Periodontology 71: 1528–34.
Quist-Paulsen, P. 2010. Statins and inflammation: an update. Current Opinion in Cardiology 25: 399–405.
Horiuchi, N., and T. Maeda. 2006. Statins and bone metabolism. Oral Diseases 12: 85–101.
Mundy, G., R. Garrett, S. Harris, J. Chan, D. Chen, G. Rossini, et al. 1999. Stimulation of bone formation in vitro and in rodents by statins. Science 286: 1946–9.
Lindy, O., K. Suomalainen, M. Makela, and S. Lindy. 2008. Statin use is associated with fewer periodontal lesions: a retrospective study. BMC Oral Health 8: 16.
Saxlin, T., L. Suominen-Taipale, M. Knuuttila, P. Alha, and P. Ylostalo. 2009. Dual effect of statin medication on the periodontium. Journal of Clinical Periodontology 36: 997–1003.
Saver, B.G., P.P. Hujoel, J. Cunha-Cruz, and G. Maupome. 2007. Are statins associated with decreased tooth loss in chronic periodontitis? Journal of Clinical Periodontology 34: 214–9.
Meisel, P., H.K. Kroemer, M. Nauck, B. Holtfreter, and T. Kocher. 2014. Tooth loss, periodontitis, and statins in a population-based follow-up study. Journal of Periodontology 85: e160–8.
Sangwan, A., S. Tewari, H. Singh, R.K. Sharma, and S.C. Narula. 2013. Periodontal status and hyperlipidemia: statin users versus non-users. Journal of Periodontology 84: 3–12.
Fentoglu, O., B.K. Koroglu, H. Hicyilmaz, T. Sert, M. Ozdem, R. Sutcu, et al. 2011. Pro-inflammatory cytokine levels in association between periodontal disease and hyperlipidaemia. Journal of Clinical Periodontology 38: 8–16.
Suresh, S., S. Narayana, P. Jayakumar, U. Sudhakar, and V. Pramod. 2013. Evaluation of anti-inflammatory effect of statins in chronic periodontitis. Indian Journal of Pharmacology 45: 391–4.
Ebersole, J.L., R.E. Singer, B. Steffensen, T. Filloon, and K.S. Kornman. 1993. Inflammatory mediators and immunoglobulins in GCF from healthy, gingivitis and periodontitis sites. Journal of Periodontal Research 28: 543–6.
Stashenko, P., J.J. Jandinski, P. Fujiyoshi, J. Rynar, and S.S. Socransky. 1991. Tissue levels of bone resorptive cytokines in periodontal disease. Journal of Periodontology 62: 504–9.
de Araujo Junior, R.F., T.O. Souza, L.M. de Moura, K.P. Torres, L.B. de Souza, S. Alves Mdo, et al. 2013. Atorvastatin decreases bone loss, inflammation and oxidative stress in experimental periodontitis. PloS One 8, e75322.
Moore, K.W., A. O’Garra, R. de Waal Malefyt, P. Vieira, and T.R. Mosmann. 1993. Interleukin-10. Annual Review of Immunology 11: 165–90.
Cassatella, M.A., L. Meda, S. Bonora, M. Ceska, and G. Constantin. 1993. Interleukin 10 (IL-10) inhibits the release of proinflammatory cytokines from human polymorphonuclear leukocytes. Evidence for an autocrine role of tumor necrosis factor and IL-1 beta in mediating the production of IL-8 triggered by lipopolysaccharide. Journal of Experimental Medicine 178: 2207–11.
Lacraz, S., L.P. Nicod, R. Chicheportiche, H.G. Welgus, and J.M. Dayer. 1995. IL-10 inhibits metalloproteinase and stimulates TIMP-1 production in human mononuclear phagocytes. Journal of Clinical Investigation 96: 2304–10.
Li, J.J., and C.H. Fang. 2005. Effects of 4 weeks of atorvastatin administration on the antiinflammatory cytokine interleukin-10 in patients with unstable angina. Clinical Chemistry 51: 1735–8.
Tekin, A., N. Sezgin, M.T. Katircibasi, G. Tekin, Y. Colkesen, A.T. Sezgin, et al. 2008. Short-term effects of fluvastatin therapy on plasma interleukin-10 levels in patients with chronic heart failure. Coronary Artery Disease 19: 513–9.
Sorsa, T., L. Tjaderhane, Y.T. Konttinen, A. Lauhio, T. Salo, H.M. Lee, et al. 2006. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Annali Medici 38: 306–21.
Steinberg, D., S. Parthasarathy, T.E. Carew, J.C. Khoo, and J.L. Witztum. 1989. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. New England Journal of Medicine 320: 915–24.
Davignon, J., R.F. Jacob, and R.P. Mason. 2004. The antioxidant effects of statins. Coronary Artery Disease 15: 251–8.
Loe, H., and J. Silness. 1963. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontologica Scandinavica 21: 533–51.
Silness, J., and H. Loe. 1964. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condition. Acta Odontologica Scandinavica 22: 121–35.
Ainamo, J., and I. Bay. 1975. Problems and proposals for recording gingivitis and plaque. International Dental Journal 25: 229–35.
Suzuki, K., H. Ota, S. Sasagawa, T. Sakatani, and T. Fujikura. 1983. Assay method for myeloperoxidase in human polymorphonuclear leukocytes. Analytical Biochemistry 132: 345–52.
Laufs, U., V. La Fata, J. Plutzky, and J.K. Liao. 1998. Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 97: 1129–35.
Cunha-Cruz, J., B. Saver, G. Maupome, and P.P. Hujoel. 2006. Statin use and tooth loss in chronic periodontitis patients. Journal of Periodontology 77: 1061–6.
de Lima Oliveira, A.P., M. de Faveri, L.C. Gursky, M.J. Mestnik, M. Feres, A.D. Haffajee, et al. 2012. Effects of periodontal therapy on GCF cytokines in generalized aggressive periodontitis subjects. Journal of Clinical Periodontology 39: 295–302.
Cao, C.F., and Q.T. Smith. 1989. Crevicular fluid myeloperoxidase at healthy, gingivitis and periodontitis sites. Journal of Clinical Periodontology 16: 17–20.
Nizam, N., P. Gumus, J. Pitkanen, T. Tervahartiala, T. Sorsa, and N. Buduneli. 2014. Serum and salivary matrix metalloproteinases, neutrophil elastase, myeloperoxidase in patients with chronic or aggressive periodontitis. Inflammation 37: 1771–8.
Dalcico, R., A.M. de Menezes, O.B. Deocleciano, R.B. Oria, M.L. Vale, R.A. Ribeiro, et al. 2013. Protective mechanisms of simvastatin in experimental periodontal disease. Journal of Periodontology 84: 1145–57.
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The present study was financially supported by the Hacettepe University Scientific Research Projects Coordination Unit (Grant no: 011D10201002).
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Cicek Ari, V., Ilarslan, Y.D., Erman, B. et al. Statins and IL-1β, IL-10, and MPO Levels in Gingival Crevicular Fluid: Preliminary Results. Inflammation 39, 1547–1557 (2016). https://doi.org/10.1007/s10753-016-0390-7
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DOI: https://doi.org/10.1007/s10753-016-0390-7