The amount of free corticosterone is increased during lipopolysaccharide-induced fever.
The relation between lipopolysaccharide (LPS)-induced fever and bioavailability of corticosterone (B) was examined in male Wistar rats. Animals were injected with LPS (2.5 mg/kg i.p.) or saline and core temperature and heart rate were monitored continuously using a biotelemetry system. Blood samples were withdrawn from freely moving rats via jugular catheters for estimation of total and free plasma B. LPS induced a long-lasting increase (24-48 h) in core temperature and B secretion and a short-lasting increase (90 min) in heart rate. LPS-induced fever was accompanied by a significant increase in the free/total B ratio. In contrast, an acute injection of B, which resulted in circulating B levels similar to those found after LPS, did not affect the free/total B ratio. The important role of LPS-induced fever in the hormone secretion pattern and the equilibrium between free and total B was further demonstrated in an in vitro study showing that an increase in the temperature by 3 degrees C elevated the free B fraction and the free/total B ratio of plasma samples with concentrations of B in the physiological range (5-40 microg/dl). Taken together, these findings indicate that during LPS-induced fever there is an increase in the amount of biologically available B. Exposure of glucocorticoid-sensitive targets to elevated levels of free B could contribute to the restoration of homeostasis that is disturbed during inflammation.
Cabrera
R
R
Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug Research, Sylvius Laboratories, University of Leiden, The Netherlands. rcabrera@lab.cricyt.edu.ar
Korte
S M
SM
Lentjes
E G
EG
Romijn
F
F
Schönbaum
E
E
De Nicola
A
A
De Kloet
E R
ER
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D005334:Fever / Q000097:blood*; D006339:Heart Rate / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D008070:Lipopolysaccharides; D003345:Corticosterone