INTERLEUKIN-1-BETA AND PROSTAGLANDIN-E ARE INVOLVED IN THE RESPONSE OF PERIODONTAL CELLS TO MECHANICAL-STRESS INVIVO AND INVITRO

Cytokines are local mediators released by cells of the immune system in response to stimulation by a variety of agents. These polypeptides may interact directly or indirectly with bone cells. The objectives of this study were (1) to localize prostaglandin E (PGE) and the cytokine interleukin-1-beta (IL-1-beta) in the periodontal ligament after the application of mechanical force to teeth in vivo and (2) to determine the effects of mechanical stress or IL-1-beta (or the two in combination) on PGE synthesis and bone resorption by fibroblasts in the human periodontal ligament (PDL). In 24 female cats, one maxillary canine was tipped distally by 80 gm force for 12 hours, 24 hours, or 7 days. PGE and IL-1-beta were localized immunohistochemically in serial jaw sections, and semiquantitation of cellular-staining intensity was done by microphotometry. Unstressed periodontal ligament cells stained mildly for PGE and IL-1-beta, but the staining intensity increased significantly in sites of tension. Human periodontal ligament fibroblasts were preincubated with mechanical stress and/or IL-1-beta in the presence or absence of indomethacin for 1 hour. Then the media were replaced by BGJ(b) (Fitton-Jackson modification) medium (GIBCO), and incubation was continued for 4, 8, or 24 hours in conditioned media. PGE concentrations in conditioned media were determined by radioimmunoassay, and bone-resorbing activity in conditioned media was assessed by Ca-45 release from prelabeled neonatal mouse calvaria. The conditioned media derived from cells stimulated by mechanical stress plus IL-1-beta caused significantly more bone resorption than the conditioned media obtained from cells that had been treated by each factor alone. The addition of indomethacin did not inhibit bone resorption completely. These results demonstrate that periodontal ligament cells respond to mechanical stress by increased production of PGE, and that IL-1-beta enhances this response.