Central nitric oxide participates in the lipopolysaccharide‐induced tolerance in periodontal tissues of rats

Abstract

Endotoxin tolerance is defined as an attenuation of the febrile response to repeated administrations of LPS. In this study, we tested the hypothesis that LPS tolerance occurs after repeated local injection of LPS into the periodontium of rats and that nitric oxide plays a role in this tolerance. Rats were given a gingival injection of saline or LPS (100 μg/kg) on 3 days. Body temperature was measured with a datalogger. Another group was treated with L‐NMMA, 500μg/rat i.c.v. 30 min before LPS in the 3rd day. Fos immunohistochemistry was performed 3 h after the injections in non‐tolerant rats (day 1) and in tolerant rats (day 3), after i.c.v. saline or L‐NMMA. On day 1 we observed a polyphasic febrile response after LPS injection, on day 2 this response was sensitized and on day 3 it was completely abolished, characterizing the development of LPS tolerance. This tolerance could be prevented with the pretreatment with L‐NMMA (p<0.05). Additionally, immunohistochemistry detected a reduction in LPS‐induced Fos‐like expression in the caudal subnuclei of the spinal trigeminal nucleus and in the preoptic area of hypothalamus in tolerant rats compared with non‐tolerant rats, and an enhanced of Fos positive cells in both areas after the reversion of tolerance with L‐NMMA (p<0.05). These results indicate that the LPS tolerance may occur locally in the oral cavity and central NO plays a role in this mechanism. Finantial support: FAPESP.