Correlations of norepinephrine release in the paraventricular nucleus with plasma corticosterone and leptin after systemic lipopolysaccharide: blockade by soluble IL-1 receptor.

The purpose of the study was to investigate the effects of systemic lipopolysaccharide (LPS) on norepinephrine (NE) release in the paraventricular nucleus (PVN) and on plasma concentrations of corticosterone and leptin. Soluble IL-1 receptor (sIL-1R) was used to determine the role of interleukin-1 (IL-1) in these effects. Adult male rats were implanted with a push-pull cannula in the PVN and a jugular catheter to facilitate blood sampling. On the day of the experiment, after the collection of a pretreatment blood and perfusate sample, rats were injected (i.p.) with the vehicle for LPS (saline), 2.5 or 10 microg/kg BW LPS. Other groups of animals were treated i.p. with 25 microg of sIL-1R, or a combination of 10 microg/kg BW of LPS and 25 microg of sIL-1R, 5 min before and 90 min after LPS. Blood and perfusate samples were collected at 30-min intervals for 6 h. NE concentrations in the perfusate were measured using HPLC-EC and corticosterone and leptin levels in the plasma were measured using radioimmunoassay. NE release in the PVN was dose dependent and increased significantly within 90 min in response to the high dose of LPS and reached maximum levels around 180 min before declining gradually to pretreatment levels at 330 min. The corticosterone profile in LPS-treated animals was similar to the NE release profile in the PVN. In contrast, the LPS-induced increase in leptin levels reached a maximum at 210 min and remained elevated even at the end of the observation period. Treatment with sIL-1R completely blocked the LPS-induced effects. It is concluded that LPS stimulates NE release in the PVN and increases plasma concentrations of corticosterone and leptin and that these effects are mediated at least in part by IL-1.