Radiodetoxified lipopolysaccharide fails to activate the hypophyseal-pituitary-adrenal axis in the rat

Lipopolysaccharide (LPS) is known to raise the concentration of the circula ting stress hormones such as ACTH, corticosterone and P-endorphin. This eff ect of endotoxin is mediated by different immune system-released hormone-li ke factors (e.g. interleukins, tumor necrosis factor etc.). Gamma-ray irrad iation of LPS alters its biological properties and results in a radiodetoxi fied LPS preparation with numerous beneficial effects and decreased toxicit y. In this study we compared the neuroendocrine effects of a commercial LPS and our native and radiodetoxified LPS preparations in rats. Plasma ACTH, corticosterone and P-endorphin levels were measured by specific radioimmuno assays 120 min after intraperitoneal LPS administration. Control animals we re injected with saline. Results show a dramatic increase in all hormones a fter administration of commercial and our native LPS preparation. Hormone l evels in saline-injected controls and radiodetoxified LPS-treated rats did not rise significantly. These results suggest that radio-detoxification dis integrated that part of the LPS molecule complex which is responsible for t oxicity including an enhanced production of cytokines, which trigger the hy pothalamopituitary-adrenal axis. Copyright (C) 2000 S. Karger AG, Basel.