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 mug/kg lipopol ysaccharide (LPS) into artificial subcutaneous chambers and analysed under the influence of the local anesthetic, ropivacaine (ROPI), which was admini stered into the chamber at a dose of 10 mg/kg 30 min prior to LPS. In respo nse to injections of 100 mug/kg LPS into the subcutaneous chambers, fever w as not modified by pretreatment with ROPI. High amounts of bioactive tumor necrosis factor (TNF) alpha and interleukin-6 (IL-6) were measured in the l avage of the chambers after administration of LPS. Comparatively low concen trations of both cytokines (0.5-4% of the concentrations in the lavage flui d) were detected in blood plasma simultaneously. In response to injections of 10 mug/kg LPS into the subcutaneous chambers, fever was significantly re duced by pretreatment with ROPI to about 60% of the febrile response of con trol 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 suppr ession of fever by the local anesthetic was not observed when ROPI was subc utaneously injected into the contralateral site of the chamber position so that a systemic effect of ROPI in the reduction of fever can be excluded. T he results indicate a participation of afferent neural signals in the manif estation of fever. This effect becomes obvious only if the dose of the appl ied inflammatory stimulus (LPS) is not high enough to activate a systemic g eneralised inflammatory response. (C) 2000 Elsevier Science Inc. All rights reserved.