Afferent nerves are involved in the febrile response to injection of LPS into artificial subcutaneous chambers in guinea pigs.

In guinea pigs, fever was induced by injections of 100 or 10 microgram/kg lipopolysaccharide (LPS) into artificial subcutaneous chambers and analysed under the influence of the local anesthetic, ropivacaine (ROPI), which was administered into the chamber at a dose of 10 mg/kg 30 min prior to LPS. In response to injections of 100 microgram/kg LPS into the subcutaneous chambers, fever was not modified by pretreatment with ROPI. High amounts of bioactive tumor necrosis factor (TNF) alpha and interleukin-6 (IL-6) were measured in the lavage of the chambers after administration of LPS. Comparatively low concentrations of both cytokines (0.5-4% of the concentrations in the lavage fluid) were detected in blood plasma simultaneously. In response to injections of 10 microgram/kg LPS into the subcutaneous chambers, fever was significantly reduced by pretreatment with ROPI to about 60% of the febrile response of control animals. Levels of TNF and IL-6 were lower in response to the reduced dose of LPS. TNF in plasma was even below the limit of detection. The suppression of fever by the local anesthetic was not observed when ROPI was subcutaneously injected into the contralateral site of the chamber position so that a systemic effect of ROPI in the reduction of fever can be excluded. The results indicate a participation of afferent neural signals in the manifestation of fever. This effect becomes obvious only if the dose of the applied inflammatory stimulus (LPS) is not high enough to activate a systemic generalised inflammatory response.