Lipopolysaccharide stimulates norepinephrine efflux from the rat hypothalamus in vitro: blockade by soluble IL-1 receptor.

Lipopolysaccharide (LPS) has been shown to produce a number of central and neuroendocrine effects. While all mechanisms are not clear, it is believed that central catecholamines could be involved in this process. This study was done to investigate the direct effects of LPS on norepinephrine (NE) efflux from the medial basal hypothalamus in adult male rats using a combination of an in vitro incubation system and high performance liquid chromatography with electrochemical detection. Basal NE efflux was determined by incubating the hypothalami with Krebs Ringers Henseleit (KRH) alone for 60 min. Then, the hypothalami were incubated with KRH alone (control) or KRH containing 100 ng or 200 ng of LPS, 15 microg of soluble IL-1 receptor (sIL-1R) or a combination of 200 ng LPS and 5 or 15 microg of sIL-1R. In the third incubation period, the hypothalami were incubated with KRH alone to check for the residual effects of LPS if any. In the fourth incubation period, the hypothalami were incubated with high K+KRH to check for tissue viability. Incubation with LPS stimulated NE efflux in a dose-dependent manner. Incubation of hypothalami with 200 ng of LPS and 15 microg of sIL-1R completely blocked LPS-induced increase in NE efflux. These results indicate that LPS could act directly on the hypothalamus to stimulate the efflux of NE and this effect is probably mediated through IL-1.