Effects of Tumor Necrosis Factor-α Inhibitors Pentoxifylline and Thalidomide on Alveolar Bone Loss in Short-Term Experimental Periodontal Disease in Rats.

Abstract

Pentoxifylline (PTX) and thalidomide (TLD) have been shown to inhibit cytokine synthesis, mainly tumor necrosis factor (TNF)-α, in different inflammatory conditions. We studied the effects of these cytokine inhibitors in an experimental model of periodontitis. Wistar rats were subjected to a ligature placement around the second upper right molars. Alveolar bone loss was evaluated by the sum of the distances between the cusp tip and the alveolar bone along the axis of each molar root, subtracting from the contralateral side. Histopathological analysis was based on cell influx, amount of alveolar bone, and cementum integrity. Animals were weighed daily, and total and differential peripheral white blood cell counts were performed at 6 hours and 1, 7, and 11 days after induction of periodontitis. Groups were treated with saline (positive control), PTX, or TLD 1 hour before and daily up to 11 days after induction of periodontitis. Alveolar bone loss was inhibited 42%, 54%, and 69% by PTX at 5, 15, and 45 mg/kg, and 25%, 25%, 42%, and 54% by TLD at 5, 15, 45, and 90 mg/kg, respectively, as compared to the control (P <0.05; analysis of variance). Histological analysis showed that PTX and TLD reduced cell influx and alveolar bone and cementum destruction. PTX and TLD also reversed peripheral lymphomonocytosis but not weight loss, as compared to controls. These data showed that both PTX and TLD reduced alveolar bone loss in periodontitis. The data showed a protective effect of PTX and TLD on experimental periodontitis, suggesting a role for TNF-α in the pathophysiology of periodontitis. J Periodontol 2004;75:162-168.