Resolvin D1 (RvD1; 7S, 8R, 17S trihydroxy-4Z, 9E, 11E, 13Z, 15E, 19Z-docosahexaenoic acid) is a newly identified lipid mediator with potent anti-inflammatory and pro-resolving properties derived from docosahexaenoic acid (DHA). RvD1 provides protection against tissue damage in several systemic inflammation models. The purpose of this study was to evaluate the proresolving actions of topically applied RvD1 in experimental periodontitis compared to vehicle control.
Methods:
Periodontitis was induced with ligature and P.gingivalis in 26 New Zealand White rabbits over 6 weeks. Five animals were sacrificed at 6 weeks to determine extent of periodontal disease. The remaining 21 animals were divided into 3 treatment groups: 1=no-treatment (n=3); 2=vehicle (n=13); 3=RvD1 (n=5). Topical application (4µg/site) of RvD1/vehicle was performed three times a week for an additional 6 weeks. Morphometric, radiographic and histologic evaluations were performed. Bone loss was measured directly on defleshed jaws. Histologic sections were stained with hematoxylin-eosin and tartrate-resistant acid phosphatase for descriptive histology and osteoclastic activity.
Results:
In response to P. gingivalis, rabbits developed periodontal inflammation characterized by soft tissue and bone loss. During the treatment phase, significant disease progression was detected in untreated and vehicle groups with prominent leukocyte infiltration and additional bone loss. Local RvD1 application reduced the inflammatory changes and osteoclastic activity induced by P. gingivalis (p<0.01). RvD1 treatment resulted in significant bone gain (>95%) compared to vehicle with complete resolution of inflammatory changes and bone fill (p<0.01). The results demonstrate that RVD1 displays similar actions in resolution of periodontal inflammation and tissue regeneration to EPA-derived lipid mediator, RvE1 (Hasturk et al., J.Immunol. 2007).
Conclusions:
In a rabbit model of human periodontal disease, local application of RvD1 a novel pro-resolving lipid mediator in small amounts results in complete resolution of inflammation and regeneration of bone. Supported by USPHS Grant DE16191.