Discussion.
Although periapical granulomas occur commonly, the pathological mechanisms that are responsible for their expansion have not been fully established. Periapical bone resorption is a prominent feature of periapical lesion development and various kinds of inflammatory mediators, including IL-1and TNF-and other bone resorptive cytokines, were determined in the exudate of periapical lesions (Matsuo et al. 1994, Takayama et al. 1996). From in vitro studies, IL-1has been found to be 500-fold more potent than TNF-in mediating bone resorption and constitutes the major component of osteoclast activating factor (Stashenko et al. 1987, Stashenko et al. 1989). Although these findings indicate that IL-1may be more relevant with respect to periapical bone resorption, the relative concentration of TNF-actually present in periapical exudate has not yet been determined. In this respect, by immunoassay of periapical exudates from canals, we determined IL-1and TNF-levels.
Both cytokines, IL-1and TNF-are mainly produced by cells belonging to the mononuclear phagocyte system and cells positively stained for IL-1and TNF-have been demonstrated in periapical granulomas (Artese et al. 1991). In the present study, IL-1was detected in all of the periapical exudate samples, whereas TNF-was found in 25 of 35 samples. IL-1was present in approximately 12-fold greater quantities than TNF-. Furthermore, IL-1levels were significantly higher in periapical exudates of teeth with larger radiolucent areas. Therefore, on the basis of greater quantity in periapical exudate of larger lesions, as well as potency in stimulating bone resorption, we conclude that of these mediators, IL-1is likely to be of greater importance in periapical bone loss.
In studies attempting to correlate IL-1levels and clinical findings, conflicting results have been reported. Lim et al. (1994) demonstrated that symptomatic human periradicular lesions showed a trend to contain more IL-1levels than asymptomatic lesions. Matsuo et al. (1994) could not find any significant difference of IL-1levels when the exudates were divided into two groups according to the presence of similar clinical findings used in this study. Kuo et al. (1998) have reported higher concentrations of IL-1in the exudates collected from teeth with suppuration. In this study, we could not determine significantly higher IL-1levels when the clinical findings were present. Pus discharging canals contained approximately 3-fold higher IL-1levels than nondischarging canals. However, the difference between groups was not statistically significant, probably due to our small sample size for pus discharging canals and distribution of data in wide range.
Detectable levels of TNF-levels in the periapical exudates were determined by Safavi & Rossomando (1991). Artese et al. (1991) located cells stained positively for TNF-in periapical granulomas, suggesting its bone resorptive role in the pathogenesis of periapical granulomas. To our knowledge, this is the first study evaluating the association between periapical exudate TNF-levels and clinical findings. Data obtained from this study revealed that TNF-levels were relatively low when compared to IL-1levels and there was no correlation between these cytokines. Interestingly, TNF-levels negatively correlated with exudate volume and tended to be lower in the presence of clinical findings. These findings suggest that TNF-levels in the periapical exudates are not reflecting inflammatory conditions. In a tissue culture study, Stashenko et al. (1987) have demonstrated a synergistic interaction between IL-1and TNF-in bone resorbing activity. Nevertheless, we are not able to determine such a synergy and our results suggest that, at least, it is not operative in periapical bone resorption.

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