Effects of etanercept, a tumour necrosis factor‐α antagonist, in an experimental model of periodontitis in rats

Abstract

Background and purpose: Etanercept is a tumour necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate, for the first time, the therapeutic efficacy of in vivo inhibition of TNF-a in an experimental model of periodontitis. Experimental approach: Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Etanercept was administered at a dose of 5 mg kg À1 , s.c., after placement of the ligature. Key results: Periodontitis in rats resulted in an inflammatory process characterized by oedema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators, tissue damage, apoptosis and disease. Treatment of the rats with etanercept (5 mg kg À1 , s.c., after placement of the ligature) significantly reduced the degree of (1) periodontitis inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) iNOS (the expression of nitrotyrosine and cytokines (eg TNF-a)) and (4) apoptosis (Bax and Bcl-2 expression). Conclusions and Implications: Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury, events associated with periodontitis.

LPS-Induced Inhibition of Osteogenesis Is TNF-α Dependent in a Murine Tooth Extraction Model

“…A time course study of the serum TNF-a level (Fig. 3A) suggested that high levels of serum TNF-a would persist during the period (days 0-14) after tooth extraction, whereas the TNF-a level might be decreasing to a level <50 pg/ml during the late period after tooth extraction (days [14][15][16][17][18][19][20][21]. The significant reduction of serum osteocalcin level by LPS injection in WT mice appeared on day 7 not on day 21 after tooth extraction (Figs.…”

“…(7)(8)(9) In addition, TNF-a plays a central role in bone pathophysiology. (10) Although the relationship between TNF-a and bone resorption is well characterized, (11)(12)(13)(14)(15)(16) the connection between TNF-a and bone formation remains to be elucidated.…”

Etanercept protects remote organ damage in a rat model of thermal injury

“…Di Paola et al demonstrated that treatment with etanercept attenuates; TNF- activity, the infiltration of neutrophils, cell apoptosis, the iNOS, and nitrotyrosine formation. According to the findings, Di Paola et al suggest that interventions which may reduce the generation of TNF-, may be useful in conditions associated with local or systemic inflammation (40).…”

Host‐response: understanding the cellular and molecular mechanisms of host‐microbial interactions – Consensus of the Seventh European Workshop on Periodontology

“…In periodontitis, therapies targeting TNF-a and IL-1b have demonstrated efficacy in animal models (Zhang et al 2004, Di Paola et al 2007, however no human studies have been reported. Interestingly, a limited number of small studies report on periodontal status in RA patients undergoing treatment for RA: TNF-a inhibition in these patients with RA was reported to either enhance, or have no effect on gingival inflammation, although reduced alveolar bone loss was noted.…”