Reduced central c-fos expression and febrile response to repeated LPS injection into periodontal tissue of rats.

Systemic injection of repeated doses of Escherichia coli lipopolysaccharide (LPS) results in attenuation of the febrile response, i.e. endotoxin tolerance, which has been fairly well characterized in rats. In the present study, we tested the hypothesis that endotoxin tolerance also occurs after repeated local injection of LPS into periodontal protection tissue. Male Wistar rats were given a gingival intra-pouch injection of sterile saline or LPS at dose of 100 microg/kg on three consecutive days. Body core temperature (Tb) was measured with a miniature datalogger. Another group of animals were used for Fos immunohistochemistry 3 h after the injections in both non-tolerant and tolerant animals. On day one we observed a polyphasic febrile response after LPS injection. The increase in body temperature started about 2 h after LPS administration and lasted 5 h. On day two this response was sensitized and on day three the febrile response was completely abolished. These data suggest that rats develop endotoxin tolerance after repeated LPS administrations into tissues within the oral cavity. Moreover, immunohistochemistry detected a reduction in LPS-induced Fos-like immunoreactivity expression in the subnucleus caudalis of spinal trigeminal nucleus and in the preoptic area of the hypothalamus (POA) in tolerant rats compared with non-tolerant animals, indicating that the endotoxin tolerance may be locally mediated in the periodontal protection tissues of rats.

New role of the trigeminal nerve as a neuronal pathway signaling brain in acute periodontitis: participation of local prostaglandins.

The systemic induction of cytokines and prostaglandins plays a key role in the development of fever. However, whether fever is triggered by local injection of lipopolysaccharide (LPS) and the involvement of locally produced prostaglandins in periodontal tissue has never been assessed. Thus, we tested the hypothesis that the trigeminal nerve is a neuronal pathway that signals the brain during acute periodontitis, and this response involves prostaglandin induction. Rats were given a gingival intra-pouch injection of sterile saline or Escherichia coli lipopolysaccharide, at doses of 10 and 100 microg/kg. Some animals were pre-treated with the local anesthetic mepivacaine or had the peripheral branches of the trigeminal nerves transected. Another group of animals were pre-treated (locally or systemically) with the nonselective inhibitor of cyclooxygenases diclofenac. Body core temperature (T (b)) was measured by means of biotelemetry before and after injections. LPS elicited a dose-dependent increase in T (b), which was abolished by mepivacaine, bilateral transection of the peripheral branches of the trigeminal nerve, or local treatment with diclofenac. The results indicate that there is an activation of periodontal nerves to induce fever by LPS. It also shows that local formation of prostaglandins plays a role in fever development. Moreover, immunohistochemistry detected c-fos expression in the subnucleus caudalis of spinal trigeminal nucleus and in the preoptic area of the hypothalamus 2 and 3 h after LPS injection, further confirming the role of trigeminal nerve signaling brain in acute periodontitis.