Individual variation in hypothalamus-pituitary-adrenal responsiveness of rats to endotoxin and interleukin-1β

Intraperitoneal (ip) administration of lipopolysaccharide (LPS) or interleukin (IL)-1 beta induces activation of the hypothalamus-pituitary-adrenal (HPA) axis. In some experiments, a marked individual variation has been observed in HPA responses to these stimuli. We reasoned that only parameters that correlate with this variability may reflect signals involved in HPA activation. Although IL-1 beta is found in the peritoneal cavity and has been implicated in the HPA response to ip LPS, IL-1 beta levels in peritoneal lavage fluid did not correlate with the variation in HPA responsiveness and neither did IL-1 beta concentrations in plasma. In contrast, IL-6 concentrations in plasma, but not in peritoneal lavage fluid, correlated with this variation to ip LPS or IL-1 beta. We conclude that IL-6 in the plasma represents a major determinant of the individual variation in HPA responses to ip LPS or IL-1 beta. Because of its positive correlation with Fos expression in various brain-stem nuclei, we suggest that circulating IL-6 may facilitate the generation of signals in vagal afferents or potentiate vagal information transfer to lower brain-stem nuclei.