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CYTOKINES IL-1 AND IL-6 IN GINGIVAL CREVICULAR FLUID DURING ORTHODONTIC TREATMENT, IN CHILDREN AND ADULTS. Amila Vujačić 1 , Aleksandra Konić 2 , Jasna Pavlović 1 , Nadežda Milošević-Jovčić 2 , Vladanka Vukićević 1.
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CYTOKINES IL-1 AND IL-6 IN GINGIVAL CREVICULAR FLUID DURING ORTHODONTIC TREATMENT, IN CHILDREN AND ADULTS Amila Vujačić1, Aleksandra Konić2, Jasna Pavlović1, Nadežda Milošević-Jovčić2, Vladanka Vukićević1 1University of Priština, Medical Faculty Kosovska Mitrovica,2Institute for Medical Research, University of Belgrade, Belgrade, Serbia Objectives: During orthodontic correction of tooth position the remodeling of periodontal ligament and alveolar bone occurs, in response to mechanical loading. The early phase of this process is characterized by an aseptic inflammatory response, and various proinflammatory cytokines have been suggested to play a role in it. IL-1 and IL-6 are among the first cytokines the levels of which are elevated in gingival crevicular fluid (GCF), during the application of orthodontic force. IL-1 is an inducer of IL-6, and both participate in the complex network of mediators that regulate inflammation. Although there have been a numerous studies examing the levels of various cytokines in GCF during orthodontic tooth movement, little data are available on the effect of age on cytokine production in humans. In this work the expression of IL-1 and IL-6 cytokines in gingival crevicular fluid (GCF) in children and adults, during the early phase of orthodontic treatment was examined. Materials and Methods: Patients The subjects were 10 healthy children (mean age 13 years) and 10 healthy adults (mean age 20 years), undergoing orthodontic treatment.The patients were of good general and periodontal health. GCF collection GCF was sampled at the control and treatment sites before, 24, 72, and 168 hours after initiation of orthodontic treatment. Paper strips were inserted for 60s into the gingival crevice, then transferred into the plastic tubes and stored at -70C until use. The GCF was eluted from each strip into PBS and extracted by centrifugation for 5 min at 15000 g. Cytokines levels in GCF were determined using enzyme-linked immunosorbent assay kits. The content of IL-1 and IL-6 in GCF markedly differed between the children and adults, both in control and experimental teeth. IL-1 values were far higher in control teeth of children than in adults, in all time intervals, in difference to IL-6, the values of which were lower in children than in adult control teeth. In experimental teeth, the levels of both cytokines were higher in children than in adults, and their fluctuations after treatment were more expressive. The degree of IL-6 increase in children was significantly greater than in adults. There was difference in rate of tooth movement in children and adults. The initial period (0 to 7 days) showed a faster movement for children than for adults (p< 0.003). In children, there was a positive, nonsignificant, correlation between the levels of both cytokines and the average velocity of tooth movement, while in adults such correlation was registered only for IL-1β. Results: Conclusions: IL-1 and IL-6 were increasingly expressed during initial phase of orthodontic treatment, both in children and adults, but the effects of enhanced cytokines production on tooth displacement were not the same in two groups. The results could be interpreted as follows: IL-1, the production and upregulation of which was initially induced by mechanical force, stimulated the production of IL-6, the level of which increased then at 24 hr, in relation to the control values. Relative high levels of IL-6 triggered the mechanism of feedback control resulting in decrease of IL-1 at 72 hr from the beggining of orthodontic treatment. This, then, leads to the decrease of IL-6. Further course of IL-1 and IL-6 quantitative changes could be associated with their role in the second wave of cytokine upregulation, during which they stimulate the production of other cytokines and ligandes, essential for the remodeling. Those substances inhibit further production of IL-1 and IL-6, thus stoping their proinflammatory activity Alhashimi N, Frithiof L, Brudvik P, Bakhiet M. Orthodontic tooth movement and de novo synthesis of proinflamatory cytokines. Am J Orthod Dentofacial Orthop 2001; 119: 307-312. Başaran G, Özer T, Kaya FA, Hamamci O. Interleukins 2, 6, and 8 levels in human gingival sulcus during orthodontic treatment. Am J Orthod Dentofacial Orthop 2006; 130: 7.e1-7.e6. Cavaillon J-M, Duff G. Cytokines and the cellular mechanism of inflamation. У: Thèze J (уредник) „The cytokine network and immune functions“, University Press, Oxford. 1999; 251-261. Davidovitch Z, Nicolay O, Ngan PW,Shanfeld JL. Neurotransmitters, cytokines and control of alveolar bone remodeling in orthodontics. Dent Clin North Am 1988; 32: 411-435. Dolce C, Malone JS, Wheeler TT. Current concept in the biology of othodontic tooth movement. Semin Orthodont 2002; 8: 6-12. Dudic A, Kiliaridis S, Mombelli A, Giannopoulou C. Composition changes in gingival crevicular fluid during orthodontic tooth movement: comparisons between tension and compression sides. Eur J Oral Sci 2006; 114: 416-422. References: 88th CONGRESS EOS 2012Santiago de Compostela (Spain) – 18 to 23 june 2012