Objectives: Recently, we could demonstrate in a rat model of experimentally induced root resorption that the systemic application of soluble receptors to the cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNFalpha) reduced tooth movement and the number of osteoclasts and odontoclasts. In this study, the occurrence and expression of proinflammatory molecules is investigated. Methods: Orthodontic movement of the upper left first molar was performed in 80 Wistar rats using a coil spring. Starting on day -1, three groups of 20 animals each received daily intraperitoneally injections of 2ml of 1ml/ml soluble receptors a) to IL-1(sIL-RII) b) to TNFalpha (sTNFalpha-RI) and c) a combination of a) and b). After 3, 6, 9 and 12 days, animals were killed in groups of 5 each and their maxillae prepared for further histological analysis. IL-1alpha, IL-1beta, IL-1 receptor (IL-1R), TNFalpha, TNF receptors, IL-6 and inducible nitric oxide synthase (iNOS) were detected immunohistochemically, the expression of IL-1alpha, beta, TNFalpha and IL-6 by a non-radioactive in-situ-hybridization technique. Results: In contrast to non-treated rats, immunostaining for IL-1beta, IL-1R, TNFalpha and IL-6 and stronger expression for IL-1beta and IL-6 was obvious in the periodontal ligament (PDL) of all orthodontically treated animals. No differences in distribution and expression of factors investigated were seen in animals of the different experimental groups except for IL-1beta. Expression and protein in osteoclasts and odontoclasts was almost absent in sIL1R-treated animals starting with day 6. IL-1beta immunoreactivity was also reduced in osteoclasts and odontoclasts in rats from days 9 and 12 of the double treated experimental group. Conclusion: Experimentally induced tooth movement in rats increases expression of different proinflammatory molecules in the PDL, but systematic application of soluble receptors to IL-1 and TNFalpha does not lead to obvious alterations in osteoclast regulation by cytokines, except for IL-1beta. (Supported by the DFG Ja444/3-1)

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